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Pyroptosis plays a pivotal role in airway epithelial inflammation during the progression of asthma. This study aimed to explore the influence and mechanisms of opa-interacting protein 5 antisense RNA1 (OIP5-AS1) and growth arrest-specific transcript 5 (GAS5) on pyroptosis in asthmatic models. Pyroptosis was induced in Dermatophagoides pteronyssinus 1 (Der p1)-exposed 16HBE cells and ovalbumin (OVA)-challenged rats. Subsequently, pyroptosis and its related molecular mechanisms were investigated. Our results indicated that GATA1, OIP5-AS1, GAS5, and LIFR were upregulated, while miR-136-5p was downregulated in the patients and experimental models of asthma. OIP5-AS1/GAS5 knockdown repressed NLRP3 inflammasome-mediated pyroptosis in 16HBE cells. Mechanistically, OIP5-AS1/GAS5 sponged miR-136-5p to enhance LIFR expression and subsequently activated NF-κB pathway. OIP5-AS1, GAS5, or LIFR-mediated induction of pyroptosis was abrogated by miR-136-5p mimics or NF-κB inhibitors (BAY11-7082). Finally, GATA1 transcriptionally activated OIP5-AS1/GAS5 to trigger pyroptosis, thereby driving asthma progression in vivo and in vitro. In conclusion, OIP5-AS1/GAS5 transcriptionally activated by GATA1 promoted NLRP3 inflammasome-mediated pyroptosis via the modulation of miR-136-5p/LIFR/NF-κB axis and consequently resulted in airway inflammation in asthma. Our results may provide novel therapeutic strategies for asthma., (© 2024 Federation of American Societies for Experimental Biology.)

It was previously thought that ncRNA could not encode polypeptides, but recent reports have challenged this notion. As research into ncRNA progresses, it is increasingly clear that it serves roles beyond traditional mechanisms, playing significant regulatory roles in various diseases, notably cancer, which is responsible for 70% of human deaths. Numerous studies have highlighted the diverse regulatory mechanisms of ncRNA that are pivotal in cancer initiation and progression. The role of ncRNA-encoded polypeptides in cancer regulation has gained prominence. This article explores the newly identified regulatory functions of these polypeptides in three types of ncRNA-lncRNA, pri-miRNA, and circRNA. These polypeptides can interact with proteins, influence signaling pathways, enhance miRNA stability, and regulate cancer progression, malignancy, resistance, and other clinical challenges. Furthermore, we discuss the evolutionary significance of these polypeptides in the transition from RNA to protein, examining their emergence and conservation throughout evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Post-operative cognitive dysfunction (POCD) refers to the functional impairment of the nervous system caused by prolonged exposure to anesthetics. It is known that prolonged exposure to anesthetics may increase the risk for the development of several cognitive impairments. The drugs used to induce general anesthesia are generally safe, owing to the CNS's direct and/or indirect self-protective activity against drug-induced damages. Non-coding RNAs have recently started to gain attention to better understand the mechanism of gene regulation correlated to cellular physiology and pathology. In order to provide new insights for the neuroprotective function of highly expressed ncRNAs in the central nervous system, we investigated their expression profile in the circulating exosomes of patients exposed to anesthesia vs healthy controls. The experimental design envisaged the recruitment of 30 adult patients undergoing general anesthesia and healthy controls. The effects of anesthetics have been evaluated on miR-34a and miR-124, on the lncRNAs MALAT-1, HOTAIR, GAS5, BLACAT1, HULC, PANDA, and on YRNAs. NcRNAs miR-34a, miR-124, MALAT-1, HOTAIR, GAS5, BLACAT1, and YRNA1 are significantly overexpressed following anesthesia, while YRNA5 is significantly down regulated. Some of them have neuroprotective function, while other correlate with neurological dysfunctions. Our data suggests that, during anesthesia, the toxic action of some non-coding RNAs could be compensated by other non-coding RNAs, both synthesized by the CNS or also transported into neurons from other tissues. It is reasonable to suppose a mutual action of these molecules likely to secure the CNS from anesthetics, that drive a convoluted cascade of ncRNA-dependent biological counter-responses. Our findings are novel in the field of brain dysfunction, indicating that some of the analyzed ncRNAs, although several of their functions still need to be addressed, could be suggested as potential biomarkers and therapeutic targets in post-operative cognitive dysfunction-related processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The Echiura worm Urechis unicinctus refers to a common benthic invertebrate found in the intertidal zone of Huanghai as well as Bohai Bay. U. unicinctus is known to contain various physiologically active substances, making it highly valuable in terms of its edibility, medicinal properties, and economic potential. Nonetheless, the limited study on the immune system of U. unicinctus poses difficulties for its aquaculture and artificial reproduction. Marine invertebrates, including shellfish and U. unicinctus, are thought to primarily depend on their innate immune system for disease protection, owing to the severalinnate immune molecules they possess. Herein, we employed PacBio single-molecule real-time (SMRT) sequencing technology to perform the full-length transcriptome analysis of U. unicinctus individuals under five different conditions (room temperature (RT), low temperature (LT), high temperature (HT), without water (DRY), ultraviolet irradiation (UV)). Concequently, we identified 59,371 unigenes that had a 2,779 bp average length, 2,613 long non-coding RNAs (lncRNAs), 59,190 coding sequences (CDSs), 35,166 simple sequence repeats (SSRs), and 1,733 transcription factors (TFs), successfully annotating 90.58 % (53,778) of the unigenes. Subsequently, key factors associated with immune-related processes, such as non-self-recognition, cellular immune defenses, and humoral immune defenses, were searched. Our study also identified pattern recognition receptors (PRRs) that included 17 peptidoglycan recognition proteins (PGRPs), 13 Gram-negative binding proteins (GNBPs), 18 scavenger receptors (SRs), 74 toll-like receptors (TLRs), and 89 C-type lectins (CLTs). Altogether, the high-quality transcriptome obtained data will offer valuable insights for further investigations into U. unicinctus innate immune response, laying the foundation for subsequent molecular biology studies and aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of epigenome, modulating gene expression through DNA methylation, histone modification, and/or chromosome remodeling. Dysregulated lncRNAs act as oncogenes or tumor suppressors, driving tumor progression by shaping the cancer epigenome. By interacting with the writers, readers, and erasers of the epigenetic script, lncRNAs induce epigenetic modifications that bring about changes in cancer cell proliferation, apoptosis, epithelial-mesenchymal transition, migration, invasion, metastasis, cancer stemness and chemoresistance. This review analyzes and discusses the multifaceted role of lncRNAs in cancer pathobiology, from cancer genesis and progression through metastasis and therapy resistance. It also explores the therapeutic potential of targeting lncRNAs through innovative diagnostic, prognostic, and therapeutic strategies. Understanding the dynamic interplay between lncRNAs and epigenome is crucial for developing personalized therapeutic strategies, offering new avenues for precision cancer medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The regulation of long non-coding RNAs (lncRNAs) has been implicated in the pathogenesis of sepsis-induced acute kidney injury (SI-AKI). Nevertheless, the specific roles of individual lncRNAs in this process remain unclear. This study investigated the expression of lncRNA AP001007 in lipopolysaccharide (LPS)-induced HK-2 cells and in the peripheral blood of sepsis patients. The result shows that LPS treatment downregulated the expression of AP001007 in HK-2 cells and that circulating levels of AP001007 were lower in sepsis patients. Furthermore, overexpressing AP001007 in HK-2 cells improved cell viability, mitochondrial activity, and survival when exposed to LPS. Additionally, LPS-treated HK-2 cells secreted fewer pro-inflammatory cytokines when AP001007 was overexpressed. Similar protective effects were observed in human kidney organoids (HKOs) subjected to LPS. These findings suggest that AP001007 confers protection against LPS-induced damage in HK-2 cells and HKOs, highlighting its potential as a regulator of SI-AKI., Competing Interests: Declarations Competing interests The authors declare no competing interests. Policy and ethics The described research complies with all relevant ethical regulations. The study was conducted in accordance with the declaration of Helsinki and approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (#2022KD0133), and written informed consent was obtained from all participants. All authors confirm that all methods were performed in accordance with the relevant guidelines and regulations., (© 2024. The Author(s).)

The orthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are represented by several 300-400 nucleotide long AI267901-like ESTs. We assumed that the AI267901-like ESTs belonged to the longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The transcript we found was a 2436 nucleotide polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp. The first exon was found to be 91 bp long and located in the third exon of OTP. The second exon was 2345 bp long and located in the second intron of OTP. We have shown the expression of this gene in many human tumors but as few as a single sample of normal testis. The transcript lacked significant ORFs suggesting that we discovered a new antisense cancer/testis (CT) sequence OTP-AS1 (OTP-antisense RNA 1), which belongs to the class of long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be a CT-coding gene/CT-ncRNA pair, or sense-antisense gene pair involved in regulatory interactions., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Heat stress (HS) can affect the physiology and metabolism of animals. HS-induced intestinal inflammation in pigs is a common disease, causing severe diarrhea, that can result in substantial economic losses to the pig industry, but the molecular mechanisms and pathogenicity of this disease are not fully understood. The objective of this study was to identify the differentially expressed genes (DEGs) and long noncoding RNAs (DELs) related to inflammation in the colon tissues of pigs under constant (1, 7, and 14 days) HS., Results: LncRNA and targeted gene interaction networks were constructed. GO annotation and KEGG pathway analyses were subsequently performed to determine the functions of the DEGs and DELs. The results revealed 57, 212, and 54 DEGs and 87, 79, and 55 DELs in the CON/H01, CON/H07, and CON/H14 groups, respectively. KRT85, CLDN1, S100A12, TM7SF2, CCN1, NR4A1, and several lncRNAs may be involved in regulating the development of intestinal inflammation. GO analysis indicated that the DEGs and DELs were enriched in a series of biological processes involved in the innate immune response, RAGE receptor binding, and positive regulation of the ERK1 and ERK2 cascades. KEGG pathways related to inflammation, such as the tight junction (TJ) and MAPK signaling pathways, were enriched in DEGs and DELs., Conclusions: This study have expanded the knowledge about colon inflammation-related genes and lncRNA biology in pigs under HS; analyzed the the lncRNA‒mRNA interaction for HS-induced intestinal inflammation. These results may provide some references for our understanding of the molecular mechanism of the intestinal response to HS in pig., Competing Interests: Declarations Ethics approval and consent to participate This study was carried out in compliance with the ARRIVE guidelines. The study was approved by the Animal Ethics Committee of Guangdong Ocean University, China (IACUC No. GDOU-LAE-2020-007). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs) play essential roles as oncogenic factors in cancer progression by influencing cell proliferation, apoptosis, and metastasis pathways. This study aims to investigate the expression changes of LINC01615 in prevalent cancers, explore its correlation with patient mortality rates, and introduce a novel therapeutic approach to reduce LINC01615 expression. Using The Cancer Genome Atlas (TCGA) data, the expression changes of LINC01615 in various cancers were analyzed, and its relationship with patient survival rates through Cox regression analysis weas assessed. Co-expressed pathways related to LINC01615 were identified via network analysis. Potential drugs to decrease LINC01615 expression were identified using the GSE38376 study. Besides, chitosan-coated nanoparticles were fabricated and functionalized with the identified drug, Lapatinib, to examine their effect on lung cancer cell lines and changes in LINC01615 expression. Our results indicated elevated LINC01615 expression in various common cancers, particularly in lung cancer, which was associated with poor prognosis in lung, breast, and kidney cancers. Co-expression network analysis suggested links to metastasis-related genes. Lapatinib, identified through GEO data, was found to modulate LINC01615 expression effectively. Chitosan-gold nanoparticles conjugated with Lapatinib significantly reduced LINC01615 expression in lung cancer cell lines while enhancing apoptosis rates. Therefore, these nanoparticles could be considered a promising therapeutic candidate for treating cancers with overexpression of LINC01615., Competing Interests: Declarations Conflict of Interest There are no conflicts to declare., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: LncRNAs play essential roles in multiple tumors. However, research on genome-wide lncRNA alterations and their functions in cervical cancer (CC) is limited. This study aims to explore key lncRNAs in CC progression and uncover the molecular mechanisms involved in the development of CC., Methods: In this study, we analyzed 30 tissues from CC, cervical intraepithelial neoplasia (CIN), and normal (NOR) using transcriptome sequencing and weighted gene co-expression network analysis to establish gene modules related to the NOR-CIN-CC transition. Machine learning diagnostic models were employed to investigate the role of lncRNAs in this transition. Molecular biological experiments were conducted to elucidate the potential mechanisms of CARMN in CC, with a particular focus on its transcriptional and post-transcriptional regulation of abnormal expression in CC., Results: CARMN was identified as a hub gene in two modules significantly associated with the NOR-CIN-CC transition. Analysis using ten machine learning models confirmed its critical role in this progression. The results of RNA-seq, qPCR and RNAScope performed in another cohort of 83 cervical tissues all showed that CARMN was significantly downregulated in CC. CARMN significantly enhanced the interaction between Keap1 and Nrf2, leading to increased ROS levels. The elevated ROS levels suppressed the Akt/mTOR signaling pathway, leading to autophagy arrest via autophagic flux blockade. Additionally, CARMN interacted with TFAP2α to repress MAPK13 transcription, further inhibiting the MAPK cascade. A promoter SNP (rs12517403) was found to increase CC risk (OR = 1.34, 95% CI = 1.11-1.61) and reduce CARMN expression by decreasing SP1 binding. Furthermore, the RNA binding proteins that could modulate CARMN RNA stability were also determined using RNA-pulldown assay. The results demonstrated that YBX1, a component of the coding region instability determinant (CRD)-mediated mRNA stabilization complex, promoted CARMN RNA stability. DHX9, another component of complex, acted as a scaffold to bridge YBX1 and CARMN., Conclusions: CARMN exerts an anti-cancer effect in CC progression by inhibiting the Akt-mTOR and MAPK signaling pathways. rs12517403 and the YBX1/DHX9 complex are key mechanisms influencing its transcription and stability in CC cells. CARMN represents a promising biomarker for CC diagnosis and therapeutic target., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted according to guidelines approved by the Institutional Review Board of Southeast University (No.2018ZDKYSB022). All participants signed informed consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Plasticity, a key hallmark of cancer, enables cells to transition into different states, driving tumor heterogeneity. This cellular plasticity is associated with cancer progression, treatment resistance, and relapse. Cancer stem cells (CSCs) play a central role in this process, yet the molecular factors underlying cancer cell stemness remain poorly understood. In this study, we explored the role of XIST (X-inactive specific transcript) long noncoding RNA in ovarian cancer stemness and plasticity through in silico and in vitro analyses. We found that XIST is significantly down-regulated in ovarian tumors, with low XIST expression linked to a higher stemness index and lower overall survival. Knocking down XIST in ovarian cancer cells enhanced stemness, particularly increasing mesenchymal-like CSCs, and under hypoxic conditions, it promoted epithelial-like CSC markers. Our findings suggest that XIST loss leads to CSC enrichment and cellular plasticity in ovarian cancer, pointing to potential therapeutic targets for patients with low XIST expression., Competing Interests: Competing interests statement:The authors declare no competing interest.

Microproteins synthesized through non-canonical translation pathways are frequently found within mitochondria. However, the functional significance of these mitochondria-localized microproteins in energy-intensive organs such as the heart remains largely unexplored. In this study, we demonstrate that the long non-coding RNA CD63-AS1 encodes a mitochondrial microprotein. Notably, in ribosome profiling data of human hearts, there is a positive correlation between the expression of CD63-AS1 and genes associated with cardiomyopathy. We have termed this microprotein CEAM (CD63-AS1 encoded amyloid-like motif containing microprotein), reflecting its sequence characteristics. Our biochemical assays show that CEAM forms protease-resistant aggregates within mitochondria, whereas deletion of the amyloid-like motif transforms CEAM into a soluble cytosolic protein. Overexpression of CEAM triggers mitochondrial stress responses and adversely affect mitochondrial bioenergetics in cultured cardiomyocytes. In turn, the expression of CEAM is reciprocally inhibited by the activation of mitochondrial stresses induced by oligomycin. When expressed in mouse hearts via adeno-associated virus, CEAM impairs cardiac function. However, under conditions of pressure overload-induced cardiac hypertrophy, CEAM expression appears to offer a protective benefit and mitigates the expression of genes associated with cardiac remodeling, presumably through a mechanism that suppresses stress-induced translation reprogramming. Collectively, our study uncovers a hitherto unexplored amyloid-like microprotein expressed in the human cardiomyocytes, offering novel insights into myocardial hypertrophy pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The development and egg-laying performance of hens are precisely regulated by hormones secreted by the pituitary. In this study, we performed comprehensive transcriptome sequencing of pituitary from Hy-Line Brown hens at 15, 20, 30 and 68 W of age. Through association analysis, we identified key genes and ceRNA regulatory networks related to pituitary development and egg production., Results: Based on the comprehensive transcriptome data, we identified 470 differentially expressed lncRNAs (DE-lncRNAs), 38 differentially expressed miRNAs (DE-miRNAs), and 2,449 differentially expressed mRNAs (DE-mRNAs). Time-series analysis pinpointed genes and signaling pathways that significantly influence pituitary hormone secretion at various stages. At 15 W, the high expression of GHRHR, NPY1R, and TSHR in the pituitary supports growth. At 20 and 30 W, elevated GNRHR expression sustains continuous egg production. In the late laying period, the expression of PRL may lead to a decline in egg production. Additionally, association analysis enabled the construction of a ceRNA regulatory network involving non-coding RNAs that regulate the development and reproduction of hens., Conclusion: This study elucidated the comprehensive transcriptome expression profiles of the pituitary gland during the development and egg-laying processes in Hy-Line Brown hens and constructed the associated molecular regulatory networks. These findings lay the foundation for investigating the mechanisms by which non-coding RNAs regulate pituitary hormone secretion., Competing Interests: Declarations Ethical approval All animal experiments were performed according to the Regulations for the Administration of Affairs Concerning Experimental Animals (Ministry of Science and Technology, China, 2004). The protocols and guidelines were approved by the Institutional Animal Care and Use Committee of Henan Agricultural University, China. The study was carried out in compliance with the ARRIVE guidelines. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Extracellular vesicles (EVs) are a group of nanoscale cell-derived membranous structures secreted by all cell types, containing molecular cargoes involved in intercellular communication. EVs can be used to mimic "nature's delivery system" to transport nucleic acids, peptides, lipids, and metabolites to target recipient cells. EVs offer a range of advantages over traditional synthetic carriers, thus paving the way for innovative drug delivery approaches that can be used in different diseases, including cancer. Here, by using breast cancer (BC) cells treated with the multi-kinase inhibitor sorafenib, we generated EVs enriched in specific non-coding RNAs (miR-23b-3p, miR-126-3p, and the long ncRNA GAS5) and investigated their potential impact on the aggressive properties of the BC in vitro and in vivo using zebrafish., Methods: EVs were collected from 4 different BC cell lines (HCC1937, MDA-MB-231, MCF-7, and MDA-MB-453) and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. Levels of encapsulated miR-23b-3p, miR-126-3p, and GAS5 were quantified by ddPCR. The role of the EVs as carriers of ncRNAs in vivo was established by injecting MDA-MB-231 and MDA-MB-453 cells into zebrafish embryos followed by EV-based treatment of the xenografts with EVs rich in miR-23b-3p, miR-126-3p and GAS5., Results: ddPCR analysis revealed elevated levels of miR-23b-3p, miR-126-3p, and GAS5, encapsulated in the EVs released by the aforementioned cell lines, following sorafenib treatment. The use of EVs as carriers of these specific ncRNAs in the treatment of BC cells resulted in a significant increase in the expression levels of the three ncRNAs along with the inhibition of cellular proliferation in vitro. In vivo experiments demonstrated a remarkable reduction of xenograft tumor area, suppression of angiogenesis, and decreased number of micrometastasis in the tails after administration of EVs enriched with these ncRNAs., Conclusions: Our study demonstrated that sorafenib-induced EVs, enriched with specific tumor-suppressor ncRNAs, can effectively inhibit the aggressive BC characteristics in vitro and in vivo. Our findings indicate an alternative way to enrich EVs with specific tumor-suppressor ncRNAs by treating the cells with an anticancer drug and support the development of new potential experimental molecular approaches to target the aggressive properties of cancer cells., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Bipolar disorder is a complex polygenic disorder that is characterized by recurrent episodes of depression and mania, the heterogeneity of which is likely complicated by epigenetic modifications that remain to be elucidated., Methods: We performed transcriptomic analysis of peripheral blood RNA from monozygotic (MZ) twins discordant for bipolar disorder to identify disease-associated differentially expressed long noncoding RNAs (DE-lncRNAs), which were further validated in the PsychENCODE brain RNA-seq dataset. We then performed behavioral tests, electrophysiological assays, chromatin immunoprecipitation, and PCR to investigate the function of DE-lncRNAs in the mouse and cell models. Statistical analyses were performed using GraphPad Prism 9.0 or SPSS., Results: We identified a bipolar disorder-associated upregulated long non-coding RNA (lncRNA), AP1AR-DT. We observed that overexpression of AP1AR-DT in the mouse medial prefrontal cortex (mPFC) resulted in a reduction of both the total spine density and the spontaneous excitatory postsynaptic current (sEPSC) frequency of mPFC neurons as well as depressive and anxiety-like behaviors. A combination of the results of brain transcriptome analysis of AP1AR-DT overexpressing mice brains with the known genes associated with bipolar disorder revealed that NEGR1, which encodes neuronal growth regulator 1, is one of the AP1AR-DT targets and is reduced in vivo upon gain of AP1AR-DT in mice. We further demonstrated that overexpression of recombinant Negr1 in the mPFC neurons of AP1AR-DT OE mice ameliorates depressive and anxiety-like behaviors and normalizes the reduced excitatory synaptic transmission induced by the gain of AP1AR-DT. We finally identified that AP1AR-DT reduces NEGR1 expression by competing for the transcriptional activator NRF1 in the overlapping binding site of the NEGR1 promoter region., Conclusions: The epigenetic and pathophysiological mechanism linking AP1AR-DT to the modulation of depressive and anxiety-like behaviors and excitatory synaptic function provides etiological implications for bipolar disorder., Competing Interests: Declarations Ethics approval and consent to participate All participants in this study provided informed consent prior to the study following presentation of the nature of the procedures. The study was approved by the Medical Ethics Committee of Zhujiang Hospital of Southern Medical University (#2022-KY-086) and the third People’s Hospital of Zhongshan (SSYLL20210301). The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs), which are RNA molecules longer than 200 nucleotides that do not encode proteins, are implicated in a variety of biological processes, including growth and development. Despite research into the role of lncRNAs in skeletal muscle development, the regulatory mechanisms governing ovine skeletal muscle development remain unclear. In this study, we analyzed the expression profiles of lncRNAs in skeletal muscle from 90-day-old embryos (F90), 1-month-old lambs (L30), and 3-year-old adult sheep (A3Y) using RNA sequencing. In total, 4 738 lncRNAs were identified, including 997 that were differentially expressed. Short-time series expression miner analysis identified eight significant expression profiles and a subset of lncRNAs potentially involved in muscle development. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the predicted target genes of these lncRNAs were primarily enriched in pathways associated with muscle development, such as the cAMP and Wnt signaling pathways. Notably, the expression of lncRNA GTL2 was found to decrease during muscle development. Moreover, GTL2 was highly expressed during the differentiation of skeletal muscle satellite cells (SCs) and was shown to modulate ovine myogenesis by affecting the phosphorylation levels of PKA and CREB. Additionally, GTL2 was found to regulate both the proliferation and differentiation of SCs via the PKA-CREB signaling pathway. Overall, this study provides a valuable resource and offers novel insights into the functional roles and regulatory mechanisms of lncRNAs in ovine skeletal muscle growth and development.

The redox status is intricately linked to the development and progression of cancer, a process that can be modulated by long non-coding RNAs (lncRNAs). Previous studies have demonstrated that redox regulation can be considered a potential therapeutic approach for cancer. However, the redox-related lncRNA predictive signature specific to bladder cancer (BCa) has yet to be fully elucidated. The purpose of our study is to establish a redox-related lncRNA signature to improve the prognostic prediction for BCa patients. To achieve this, we downloaded transcriptome and clinical data from the Cancer Genome Atlas (TCGA) database. Prognostic redox-related lncRNAs were identified through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis, resulting in the establishment of two risk groups. A comprehensive analysis corresponding to clinical features between high-risk and low-risk groups was conducted. Eight redox-related lncRNAs (AC018653.3, AC090229.1, AL357033.4, AL662844.4, AP003352.1, LINC00649, LINC01138, and MAFG-DT) were selected to construct the risk model. The overall survival (OS) in the high-risk group was worse than that in the low-risk group (p < 0.001). The redox-related lncRNA signature exhibits superior predictive accuracy compared to traditional clinicopathological characteristics. Gene Set Enrichment Analysis (GSEA) showed that the MAPK signaling pathway and Wnt signaling pathway were enriched in the high-risk group. Compared with the low-risk group, patients in the high-risk group demonstrated increased sensitivity to cisplatin, docetaxel, and paclitaxel. Furthermore, IGF2BP2, a potential target gene of MAFG-DT, was found to be overexpressed in tumor tissues and correlated with overall survival (OS). Our study demonstrated that the predictive signature based on eight redox-related lncRNAs can independently and accurately predict the prognosis of BCa patients., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Yaghooti grape, as the earliest grape variety in Iran, is considered as more resistant to heat, drought, and salinity than other cultivars. Cluster compactness is regarded as an inappropriate feature for the productivity of Yaghooti grape as a critical commercial and nutritional product. In plants, lncRNAs play a critical role in regulating biological processes related to growth and development. However, the potential role of lncRNAs was not assessed in cluster compactness. Totally, 1549 lncRNAs were identified by RNA-Seq data analysis in three steps of cluster formation, berry formation, and final cluster size after a thorough screening process. In addition, 229 lncRNAs were differentially expressed in the cluster development steps. Based on the functional analysis, lncRNAs are related to AG and MYB, bHLH, LBD, NAC, and WRKY TFs. Further, the target genes enrichment analysis revealed a relationship between lncRNAs with grape growth and development, as well as resistance to abiotic stresses such as heat and drought, plant defense against pathogens, and early grapes ripening. The study identified four lncRNAs as precursors of miRNAs, predicting that 112 other lncRNAs could potentially be targeted by 166 miRNAs. The results provide new insights into the regulatory functions of lncRNAs in Yaghooti grape to improve overall understanding of the molecular mechanisms related to grape compactness., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate The plant material selected was Sistan Yaghooti grape harvested from the vineyards of the University of Zabol (Agricultural Research Institute). Ethical guidelines provided by the ethics committee were followed when conducting the experiments. Consent for publication Not applicable., (© 2024. The Author(s).)

Over the past decade, substantial scientific evidence has showed that long non-coding RNAs (lncRNAs) are extensively expressed and play a crucial role in gene modulation through a diverse range of transcriptional, and post-transcriptional mechanisms. Recent discoveries have emphasized the involvement of lncRNAs in maintaining cellular homeostasis and neurogenesis in the brain. Accumulating reports identified dysregulated lncRNAs associated with psychiatric disorders, including autism. In this study, we examined the expression levels of DISC2, Linc00945, Foxg1-as1, Csnk1a1p, and Evf2 lncRNAs in blood samples from 21 clinically diagnosed autistic patients based on the Diagnostic and Statistical Manual of Mental Disorders criteria-5th edition (DSM-5), compared to age, sex, and ethnically-matched 25 healthy individuals. RNA extraction and cDNA synthesis were performed, followed by real-time PCR for quantification of lncRNAs expression levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate biomarker potential. Additionally, we investigated the correlation between gene expression levels and autism comorbidities. Our results showed a significant decrease in Csnk1a1p expression in patients with autism spectrum disorder (ASD) compared to healthy children (P value = 0.0008). ROC curve analysis indicated that Csnk1a1p expression levels could effectively discriminate patients from healthy controls (AUC = 0.837, P value = 0.000284). No significant differences were observed between Csnk1a1p expression levels and comorbidity with ADHD or intellectual disability (p-value > 0.05). Based on these findings, Csnk1a1p may play a significant role in autistic patients and could serve as a potential biomarker for diagnostic and predictive purposes, as well as a therapeutic target., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval The study protocol was approved by the ethical committee of Mashhad University of Medical Science. (IR.MUMS.MEDICAL.REC.1397.247). Consent to participate Written informed consent was obtained from the parents of participants.., (© 2024. The Author(s).)

Background: Several studies have shown that the long noncoding RNA (lncRNA) CBR3-AS1 is overexpressed in various cancers and is playing an oncogene role. This meta-analysis aims to elucidate the relationship between lncRNA CBR3-AS1 expression and the prognosis and clinicopathological features of cancer patients., Methods: A comprehensive and systematic search was conducted in PubMed, Web of Science, Cochrane Library, and EMBASE database. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were employed to evaluate the association between lncRNA CBR3-AS1 expression and clinical outcomes and clinicopathological features in cancer patients., Results: This meta-analysis finally enrolled 9 studies comprising 800 cancer patients. The combined results indicated that lncRNA CBR3-AS1 overexpression was significantly associated with shorter overall survival (pooled hazard ratios = 1.69, 95% CI 1.28-2.21, P < .001). Furthermore, elevated lncRNA CBR3-AS1 expression was closely correlated with larger tumor size (large vs small OR = 2.17, 95% CI: 1.50-3.14, P < .0001), lymph node metastasis (yes vs no OR = 2.75, 95% CI: 1.67-4.51, P < .0001), distant metastasis (yes vs no OR = 3.08, 95% CI: 1.82-5.23, P < .0001), and advanced tumour, node, metastasis stage (III/IV vs I/II OR = 2.82, 95% CI: 1.68-4.75, P < .0001)., Conclusion: Upregulated expression of lncRNA CBR3-AS1 showed significant association with unfavorable survival and indicated worse clinicopathological outcomes in multiple kinds of human cancer, and therefore might serve as a promising prognosis biomarker and therapeutic target for cancers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Vitiligo is characterized by the depletion of melanocytes due to the activation of CD8 + T cells. Taurine-upregulated gene 1 (TUG1), a long noncoding RNA, is involved in melanogenesis. This study aimed to explore the role and mechanism of TUG1 in vitiligo. RT-qPCR and western blot analyses demonstrated decreased TUG1 levels and increased miR-375 levels in patients with vitiligo. MTT and transwell assays indicated that TUG1 upregulation facilitated melanocyte survival and inhibited CD8 + T cell migration. Dual luciferase reporter and chromatin immunoprecipitation assays verified that Forkhead box O3 (FOXO3) directly interacted with the TUG1 promoter, leading to the positive regulation of TUG1 expression. In addition, FOXO3 promoted melanocyte survival by enhancing the transcription of TUG1. Luciferase reporter assay and RNA immunoprecipitation assay confirmed that TUG1 upregulated GATA binding protein 3 (GATA3) expression by targeting miR-375. TUG1 facilitated melanocyte survival by regulating the miR-375/GATA3 axis. In vitiligo, melanocyte survival is promoted by the induction of the TUG1-mediated miR-375/GATA3 axis by FOXO3, which offers new therapeutic targets for vitiligo treatment., (© 2024 Federation of American Societies for Experimental Biology.)

Colorectal cancer (CRC) is a prevalent form of malignant tumor, and the current clinical treatments are far from satisfactory. Identifying new therapeutic targets is therefore essential for clinical practices. The long intergenic non-protein coding RNA lincROR has been shown to play a significant role in the tumorigenesis of various cancers. However, the molecular mechanism underlying lincROR-mediated CRC tumorigenesis remains unclear. In the present study, we found that knockdown of lincROR significantly inhibited cell viability in vitro, while its overexpression promoted tumor growth in vivo. Mechanistically, lincROR acted as a miRNA sponge for miR-145, thereby elevating the expression of the target genes WNT2B and WNT10A. The overexpression of WNT2B and WNT10A definitely activated the Wnt/β-catenin pathway, thus led to promoting tumorigenesis in CRC. In summary, our findings identified lincROR as a novel activator of the Wnt/β-catenin pathway by serving as a miRNA sponge for miR-145 and facilitating tumorigenesis, which suggests that lincROR may be a potential therapeutic target for CRC patients., Competing Interests: All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2024 Deng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pairing of homologous chromosomes during meiosis is crucial for successful sexual reproduction. Previous studies have shown that the fission yeast sme2 RNA, a meiosis-specific long noncoding RNA (lncRNA), accumulates at the sme2 locus and plays a key role in mediating robust pairing during meiosis. Several RNA-binding proteins accumulate at the sme2 and other lncRNA gene loci in conjunction with the lncRNAs transcribed from these loci. These lncRNA-protein complexes form condensates that exhibit phase separation properties on chromosomes and are necessary for robust pairing of homologous chromosomes. To further understand the mechanisms by which phase separation affects homologous chromosome pairing, we conducted an in vitro phase separation assay with the sme2 RNA-associated proteins (Smps) and RNAs. Our findings reveal that one of the Smps, Seb1, forms condensates resembling phase separation; the observed number and size of these condensates increase upon the addition of another Smp, Rhn1, and purified RNAs. Additionally, we have found that RNAs protect Smp condensates from treatment with 1,6-hexanediol. The Smp condensates containing different types of RNA display distinct FRAP profiles, and the Smp condensates containing the same type of RNA tend to fuse together more readily than those containing different types of RNAs. Collectively, these results indicate that the specific RNA species within condensates modulate their physical properties, potentially enabling the formation of regional RNA-Smp condensates with distinct characteristics that facilitate homologous chromosome pairing., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

The role of long non-coding RNAs in fibroid pathogenesis remains largely unexplored. In a previous study, we found elevated XIST (X-inactive specific transcript) levels in fibroids, which sponged miR-29c and miR-200c, leading to the overexpression of their target genes. This study aimed to assess the therapeutic potential of XIST downregulation in fibroid treatment. Ovariectomized SCID (severe combined immunodeficiency) mice were implanted with fibroid tumors transduced with XIST siRNA or a control via lentivirus. After 1 month, animals were sacrificed and the xenografts were removed for further analysis. XIST knockdown reduced tumor weight by 15% and increased miR-29c and miR-200c expression by 3.9-fold and 2.2-fold, respectively. The mRNA expression of miR-29c targets (COL3A1, TGF-β3, CDK2, SPARC) and miR-200c targets (CDK2, FN1, TDO2), as well as PRL, E2F1, and EZH2, was significantly decreased. Protein abundance of collagen, COL3A1, FN1, CDK2, SPARC, and EZH2 was also reduced. IHC analysis of xenograft sections using the markers of Ki67 for cell proliferation and cleaved caspase 3 for apoptosis showed decreased cell proliferation and no changes in apoptosis in the XIST knockdown xenografts. This analysis also revealed decreased collagen and E2F1 staining nuclei in the XIST knockdown xenografts. These results indicate that downregulation of XIST in fibroids has beneficial therapeutic effects, by reducing tumor growth and the expression of genes involved in cell proliferation, inflammation, and extracellular matrix regulation., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objective: In this study, we performed RNA sequencing (RNA-seq) on the abdominal aorta tissue of New Zealand rabbits and investigated the potential association of lncRNA TCONS&#95;02443383 with the development of AS through bioinformatics analysis of the sequencing data. The obtained results were further validated using quantitative real-time polymerase chain reaction (qRT-PCR)., Method: We induced an AS model in New Zealand rabbits by causing balloon injury to the abdominal aorta vascular wall and administering a high-fat diet. We then upregulated the expression level of the lncRNA TCONS&#95;02443383 by injecting lentiviral plasmids through the ear vein. RNA sequencing (RNA-seq) was performed on the abdominal aorta tissues. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) analyses., Result: The overexpression of the lncRNA TCONS&#95;02443383 led to an upregulation of peroxisome proliferator-activated receptor (PPAR) signaling pathways as well as genes related to cell adhesion., Conclusion: The overexpression of the lncRNA TCONS&#95;02443383 can inhibit the occurrence and development of AS by upregulating peroxisome proliferator-activated receptor (PPAR) signaling pathways and genes related to cell adhesion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10 -15  mol/L and 1.56 × 10 -14  mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Long non-coding RNAs (lncRNAs) dysregulation is key in the pathogenesis of systemic lupus erythematosus (SLE), but the role of exosomal lncRNAs in SLE has not been well studied. We elucidated the profiles of plasma exosomal lncRNAs expression in patients with SLE and predictd their potential clinical significance in SLE., Methods: In the screening stage, six newly diagnosed and untreated patients with SLE and six healthy controls were examined by high-throughput sequencing technology, and differential exosomal lncRNA profiles were constructed. In the validation phase, two differentially selected exosomal lncRNAs from 20 patients each with active and stable SLE and 20 healthy controls were verified with RT-qPCR. The correlation between the selected exosomal lncRNAs and SLE clinical indicators was examined. The diagnostic value of the selected exosomal lncRNAs in SLE was analyzed by the receiver operator characteristic (ROC) curve., Results: Exosomes were successfully extracted from the patients and controls. Sequencing-phase sequencing demonstrated 528 upregulated lncRNAs and 7491 downregulated lncRNAs. In the validation stage, exosomal LINC00667 and DANCR were significantly upregulated in the patients, and positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Exosomal DANCR expression between the active and stable SLE patients was different. The area under the curve(AUC) of exosomal LINC00667 and DANCR for SLE diagnosis was 0.815 and 0.759, respectively., Conclusions: Exosomal LINC00667 and DANCR were upregulated in SLE, and might be new biomarkers thereof. Exosomal DANCR was associated with SLE activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

LINC00894 may be associated with synaptic function, but its biology function in neural cells is still unknown. In this study, LINC00894 knockdown decreased the EdU incorporated into newly synthesized DNA and cell viability in MTT or CCK-8 assay in HEK-293T and BE(2)-M17 (M17) neuroblastoma cells. And LINC00894 knockdown increased cellular apoptosis in Annexin V-FITC staining, the expression of activated Caspase3 and the level of reactive oxygen species (ROS) both in HEK-293T and M17 cells. Moreover, LINC00894 also protected cells from hydrogen peroxide induced apoptosis in in vitro models. Utilizing RNA sequencing (RNA-seq) integrated with quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoblot, we identified that LINC00894 affected activating transcription factor 3 (ATF3) expression in HEK-293T, M17, and SH-SY5Y neuroblastoma cells. Finally, we found that ectopic expression of ATF3 restored cell proliferation and inhibited cell apoptosis in LINC00894 downregulated M17 cells. While knockdown of ATF3 also significantly increased the cell viability inhibition and apoptosis promotion induced by LINC00894 knockdown in M17 cells. Our results from in vitro models revealed that LINC00894 could promote neuronal cell proliferation and inhibit cellular apoptosis by affecting ATF3 expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VI MV ), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VI MV , and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor cells engage with the immune system in a complex manner, utilizing evasion and adaptability mechanisms. The development of cancer and resistance to treatment relies on the ability of immune cells to adjust their phenotype and function in response to cues from the tumor microenvironment, known as immunological cell plasticity. This study delves into the role of long non-coding RNAs (lncRNAs) in enhancing immune cell flexibility in cancer, focusing on their regulatory actions in the tumor microenvironment and potential therapeutic implications. Through a comprehensive review of existing literature, the study analyzes the impact of lncRNAs on macrophages, T-cells, and MDSCs, as well as the influence of cytokines and growth factors like TNF, IL-6, HGF, and TGFβ on immunological cell plasticity and tumor immunoediting. LncRNAs exert a strong influence on immune cell plasticity through mechanisms such as transcriptional regulation, post-transcriptional modifications, and chromatin remodeling. These RNA molecules intricately modulate gene expression networks, acting as scaffolding, decoys, guides, and sponges. Moreover, both direct cell-cell interactions and soluble chemicals in the tumor microenvironment contribute to enhancing immune cell activation and survival. Understanding the influence of lncRNAs on immune cell flexibility sheds light on the biological pathways of immune evasion and cancer progression. Targeting long non-coding RNAs holds promise for amplifying anti-tumor immunity and overcoming drug resistance in cancer treatment. However, further research is necessary to determine the therapeutic potential of manipulating lncRNAs in the tumor microenvironment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Long non-coding RNA (lncRNA) plays a pivotal role in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA-miRNA regulatory network., Objectives: This research aimed to elucidate the role of lncRNA CASC11 in the delayed healing process of tibial fractures and to explore its potential regulatory mechanisms., Materials and Methods: The expression levels of CASC11 and miR-150-3p in serum samples were detected and the predictive capability of CASC11 regarding delayed healing in fracture patients. Furthermore, the study confirmed the accuracy of the binding sites between CASC11 and miR-150-3p. Subsequently, overexpression/interference plasmids of CASC11, along with overexpression plasmids co-transfected with both CASC11 and miR-150-3p, were systematically introduced into MC3T3-E1 cells to investigate their effects on the expression of osteogenic marker genes, as well as their influence on cellular proliferation and apoptosis., Results: The expression levels of CASC11 were significantly elevated, while miR-150-3p levels were markedly decreased in individuals exhibiting delayed fracture healing (P < 0.001). CASC11 was observed to suppress the expression of osteogenic marker genes, inhibit the proliferation of MC3T3-E1 cells, and promote cell apoptosis (P < 0.05). Furthermore, the overexpression of miR-150-3p effectively countered the inhibitory impact of CASC11 on osteogenic differentiation and the promoting effect on cell apoptosis (P < 0.05)., Conclusion: The sponging effect of CASC11 on miR-150-3p led to delayed fracture healing. CASC11 emerges as a potential target for treating delayed fracture healing., Competing Interests: Declarations Ethics approval and consent to participate The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Affiliated Hospital of Zunyi Medical University before the study began. The participants’ right to be informed about the study was ensured and agreed to participate in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Testicular germ cell tumor (TGCT) is a common malignant tumor in adolescents. Now, many long non-coding RNAs (LncRNAs) have been found to have an important function in TGCT. LINC00470 is specifically and highly expressed in TGCT, however, there is still no definite information concerning its role and underlying mechanism in TGCT. The purpose of this research was to look into the involvement of LINC00470 in TGCT and its intrinsic mechanism., Methods and Results: UCSC and GEPIA2 databases were used to analyze the expression of LINC00470, and the BEST website was used to perform GSEA enrichment analysis, immune infiltration analysis, and drug susceptibility analysis. SiRNA transfection was used to silence LINC00470 in TCAM-2 and NCCIT cells. Clone formation and Transwell assays were performed in TGCT cells to confirm the effects of LINC00470 on clone formation, migration, and invasion. Western Blot was performed to determine the expression of proteins related to the EMT and AKT signaling pathways. LINC00470 was specifically highly expressed in TGCT, and played a role in promoting tumor cell clone formation and cell metastasis by affecting the TGF-β and PI3K-AKT-mTOR signaling pathways to regulate the epithelial-mesenchymal transition (EMT) process; LINC00470 may also play a pro-tumor role by negatively regulating immune infiltration; in addition, the expression of LINC00470 was negatively correlated with the chemosensitivity of cisplatin in TGCT patients., Conclusions: LINC00470 may play a significant role in the etiology and metastasis of TGCT through EMT and AKT-mediated signaling pathways., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose. Ethical approval This research does not involve human or animal subjects. Consent to participate Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Since the introduction of the central dogma of molecular biology in 1958, various RNA species have been discovered. Messenger RNAs transmit genetic instructions from DNA to make proteins, a process facilitated by housekeeping non-coding RNAs (ncRNAs) such as small nuclear RNAs (snRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). Over the past four decades, a wide array of regulatory ncRNAs have emerged as crucial players in gene regulation. In celebration of Cell's 50th anniversary, this Review explores our current understanding of the most extensively studied regulatory ncRNAs-small RNAs and long non-coding RNAs (lncRNAs)-which have profoundly shaped the field of RNA biology and beyond. While small RNA pathways have been well documented with clearly defined mechanisms, lncRNAs exhibit a greater diversity of mechanisms, many of which remain unknown. This Review covers pivotal events in their discovery, biogenesis pathways, evolutionary traits, action mechanisms, functions, and crosstalks among ncRNAs. We also highlight their roles in pathophysiological contexts and propose future research directions to decipher the unknowns of lncRNAs by leveraging lessons from small RNAs., Competing Interests: Declaration of interests L.-L.C. and V.N.K. are members of the Cell advisory board., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC., Methods: The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB). CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2. Rescue experiments were applied to verify the mechanism of CASC9. Finally, the role of CASC9 was verified by xenograft modeling in vivo., Results: We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/Dox). Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9. MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2., Conclusion: CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Ganzhou People’s Hospital. All participants were provided with written informed consent at the time of recruitment, and all experiments involving human tissue specimens comply with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies in clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. Oip5-as1 may have potential as a therapeutic target for MI/R injury as its upregulated expression has been associated with reduced infarct size and improved cardiac function in animal models, although how to effectively and safely overexpress Oip5-as1 in vivo remains unclear. Lipid nanoparticles (LNPs) are a versatile technology for targeted drug delivery in numerous therapeutic applications. Herein, we aimed to assess the therapeutic efficacy and safety of LNPs coloaded with Oip5-as1 and a cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) in a murine model of MI/R injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. The structural components of LNP@Oip5-as1@CMP were physicochemically analyzed. A hypoxia/reoxygenation (H/R) model in HL-1 cells and coronary artery ligation in mice were used to simulate MI/R injury. Our results demonstrated that LNPs designed for cardiomyocyte targeting and efficient Oip5-as1 delivery were successfully synthesized. In HL-1 cells, LNP@Oip5-as1@CMP treatment significantly reduced mitochondrial apoptosis caused by H/R injury. In the murine MI/R model, the intravenous administration of LNP@Oip5-as1@CMP significantly decreased myocardial infarct size and improved cardiac function. Mechanistic investigations revealed that Oip5-as1 delivery inhibited the p53 signaling pathway. However, the cardioprotective effects of Oip5-as1 were abrogated by administrating Nutlin-3a, a p53 activator. Furthermore, no signs of major organ damage were detected after LNP@Oip5-as1@CMP injection. Our study reveals the therapeutic potential of LNPs for targeted Oip5-as1 delivery in mitigating MI/R injury. These findings pave the way for advanced targeted treatments in cardiovascular diseases, emphasizing the promise of lncRNA-based therapies.

Schizophrenia is a disabling mental disorder that affects 1% of people over their lifetime. The etiology and mechanism of schizophrenia are very complex, and many genes are involved in many different signaling pathways in the etiology of this disease. According to recent studies, one of the important mechanisms altered in this disorder is the regulation of immune system and the inflammation mechanism. In the present study, we evaluated the peripheral blood expression pattern of four lncRNAs and three protein-coding genes in the treatment- naïve patients, and medicated patients compared with sex and age-matched controls. In the medicated-patients, expression levels of IFNG, IL18RAP, AC007278.2 were significantly up-regulated (P < 0.05); and the expression level of IFNG-AS1-001 was significantly down-regulated compared to healthy controls (P < 0.05). However, levels of IL18R1, AC007278.3 and IFNG-AS1-003 were not different between these groups. In the treatment-naïve patients, IFNG, IL18R1, IL18RAP, IFNG-AS1-001, AC007278.2, and AC007278.3 were significantly up-regulated compared to controls. On the other hand, IFNG-AS1-003 was significantly down-regulated in the treatment-naïve patients compared to controls. Based on the Spearman correlation matrix, there was a significant correlation between genes in the treatment-naïve patients. We also showed the high sensitivity and specificity of IFNG-AS1-003, IFNG, IL18R1, and AC007278.3 in the identification of treatment-naïve patients from controls. The current study contributes further evidence to the understanding of the role of lncRNAs in the pathogenesis of schizophrenia. Future research is necessary to establish the validity of lncRNAs as peripheral markers for this condition., Competing Interests: Declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval This study was approved by the Medical Ethics Committee of Nanfang Hospital, Southern Medical University, and Southern Medical University Experimental Animal Ethics Committee., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs) have emerged as significant players in diverse cellular processes, including cell differentiation. Advancements in computational methodologies have facilitated the prediction of lncRNA functions, enabling insights even in non-model organisms like pathogenic parasites, in roles such as parasite development, antigenic variation, and epigenetics. In this work, we focus on the apicomplexan Toxoplasma gondii differentiation process, where the infective stage, tachyzoite, can develop into the cysted stage, bradyzoite, under stress conditions. Using a publicly available transcriptome dataset, we predicted putative lncRNA sequences associated with this differentiation process. Notably, a substantial proportion of these putative lncRNAs exhibited stage-specific expression, particularly at the bradyzoite stage. Furthermore, co-expression patterns between coding transcripts and putative TglncRNAs suggest their involvement in shared processes, such as bradyzoite development. Putative TglncRNA loci analysis revealed their potential influence on the expression of nearby coding genes, including subtelomeric genes unique to the T. gondii genome. Finally we propose a k-mer analysis approach to predict putative functional relationships between characterized lncRNAs from model organisms like Homo sapiens and the putative T. gondii lncRNAs. Our perspective led to predict putative T. gondii lncRNA that potentially could act mediating DNA damage repair pathways, opening a new study field to validate this kind of adaptive mechanisms of T. gondii in response to stress conditions., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX's role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All procedures involving experimental animals were conducted in strict accordance with the guidelines and regulations of the Experimental Animal Center at Tongji University. All animal experiments were performed following a protocol approved by the Animal Protection and Use Committee of Tongji University (Approval Number: TJAB04524105). The paraffin-embedded cancer patient samples used in this study were obtained from the affiliated Changhai Hospital of the Navy Medical University. Informed consent was obtained from all participants, and the study was approved by the Ethics Committee of the affiliated Changhai Hospital of the Navy Medical University., (© 2024. The Author(s).)

The long noncoding RNA (lncRNA) HOTAIR has been shown to act as an oncogene in a variety of cancers, including hepatocellular carcinoma (HCC). MicroRNA-122 (miR-122) is a key liver-specific miRNA that is frequently inhibited in HCC and is associated with poor prognosis. However, a potential relationship between HOTAIR and miR-122 in individual hepatocytes has not been explored. To this end, we propose here an intracellular catalytic hairpin self-assembly-CRISPR/Cas12a tandem multiplexed signal amplification strategy for the simultaneous quantification of HOTAIR and miRNA-122 in a single hepatocyte. We applied this method to analyze both normal HL-7702 liver cells and HepG2 HCC cells, and found that HL-7702 cells contained large amounts of miRNA-122, while the content of miRNA-122 in HepG2 cells was low. However, the level of HOTAIR in HepG2 cells was much higher than that in HL-7702 cells, confirming the overexpression of HOTAIR in HCC cells. We achieved the simultaneous absolute quantification of HOTAIR and miRNA-122 in single cells, providing an important method to study the relationships between these two RNA molecules in individual cells.

Neuroblastoma is the most common extra-cranial solid tumor diagnosed mostly in children below the age of five years and comprises of about 15 % of all paediatric cancer deaths. Tumor initiating cancer stem cells (CSCs) can be targeted for better treatment approaches. BASP1-AS1 is a long non coding (Lnc) RNA that is a divergent LncRNA for its coding gene brain abundant membrane attached signal protein 1 (BASP1). We had earlier demonstrated it to be expressed in foetus derived human neural progenitor cells (hNPCs), where it was a positive regulator of BASP1 and was critical for neural differentiation. In this study, we have investigated the role of BASP1-AS1 in CSCs derived from the human neuroblastoma cell line SH-SY5Y. We cultured SH-SY5Y cells on Poly-d-Lysine coated flasks in serum free media supplemented with growth factors, which led to the enrichment of CSCs as determined by marker expression. When grown on ultra-low attachment flasks, these cells formed CSCs enriched neurospheres. We examined the effects of BASP1-AS1 siRNA mediated knockdown on CSCs enriched SH-SY5Y cells and SH-SY5Y derived neurospheres. BASP1-AS1 knockdown decreased the levels of the corresponding gene BASP1 and the rate of cell proliferation of CSCs enriched cells along with low expression of Ki67. It also reduced the mRNA levels of stem cell and pluripotency gene markers (CD133, CD44, c-KIT, SOX2, OCT4 and NANOG), as also Wnt 2 and the Wnt pathway effector β catenin. It also abrogated the formation of neurospheres in ultra-low attachment flasks. A similar effect on proliferation and stemness related properties was seen on BASP1 knockdown. BASP1-AS1 and its related pathways may provide a point of intervention for the CSCs population in neuroblastoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-κB pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-α. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-α-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval All animal experiments were approved by the Animal Ethics and Welfare Committee of the Affiliated Hospital of Guangdong Medical University (No. AHGDMU-LAC-B-202304–0027)., (© 2024. The Author(s).)

Background: Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of varieties of tumors. Previous studies have shown that lncRNA GClnc1 is highly expressed in osteosarcoma (OS). However, the mechanism of lncRNA GClnc1 in osteosarcoma has not been fully elucidated. In this study, we investigated the biological roles of lncRNA GClnc1 in osteosarcoma and unveiled its underlying mechanisms., Methods: The expression of lncRNA GClnc1 in OS cells was detected by real-time quantitative PCR (qRT-PCR). The functional roles of lncRNA GClnc1 were examined by CCK8, trans-well, scratch wound healing assay, colony formation, and apoptosis assays in osteosarcoma cells upon silencing or overexpressing GClnc1. Western blot analysis, qRT-PCR, and RNA co-immunoprecipitation (RIP) assays were used to detect the interaction between lncRNA GClnc1 and NONO., Results: The expression of lncRNA GClnc1 was up-regulated in osteosarcoma cell lines. Knockdown of lncRNA GClnc1 suppressed the cell growth, migration, and invasion of OS cells, whereas the over-expression of GClnc1 improved the proliferation, migration, and invasion of OS cells. Mechanistically, we identified that lncRNA GClnc1 regulates the stability of NONO by blocking FBXW7-mediated ubiquitination degradation. Additionally, overexpression of NONO can reverse GClnc1 silencing exerted suppression of the cell proliferation, migration, and invasion, and vice versa., Conclusions: Our study elucidated that lncRNA GClnc1 participates in the progression of OS by regulating the NONO signal pathway. Targeting GClnc1 provides a potential target for future clinical treatment of OS., Competing Interests: Declarations Ethics approval and consent to participate Ethics committee belonging to the Third Affiliated Hospital of Nanchang University ratified the current study (grant number: KY2023009). The experiment was approved by the Animal Experiment Animal Use Committee of Jiangxi University of Traditional Chinese Medicine. All animal experiments were approved by the Animal Protection and Use Committee, and the experimental procedures were approved by guidelines. All methods were carried out in accordance with relevant guidelines and regulations. All methods were performed in accordance with the ARRIVE guidelines for reporting animal experiments. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated., Methods: High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR)., Results: High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in "cell metabolism," "cell adhesion," and other aspects: related gene pathways mainly involved Huntington's disease, Parkinson's disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results., Conclusion: A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future., Competing Interests: Declarations Ethical approval This study had been registered with the Chinese Clinical Trial Registration Center (ChiCTR210052331||http://www.chictr.org.cn/) on October 24, 2021. The research had also been approved by The Reproductive Medicine Ethics Committee of Shandong University of Traditional Chinese Medicine Affiliated Hospital (batch number: SDSZYYSZ20211009) and to exempt the informed consents. Human ethics and consent to participate All procedures were carried out in accordance with relevant guide-lines and regulations and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants had signed informed consent forms before enrollment. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Biosynthesis of 17β-estradiol (E2) is a crucial ovarian function in mammals, which is essential for follicular development and pregnancy outcome. Exploring the epigenetic regulation of E2 synthesis is beneficial for maintaining ovary health and the optimal reproductive traits. NORFA is the first validated sow fertility-associated long non-coding RNA (lncRNA). However, its role on steroidogenesis is elusive. The aim of this study is to investigate the regulation and underlying mechanism of NORFA to E2 synthesis in sow granulosa cells (GCs)., Results: Through Pearson correlation analysis and comparative detection, we found that NORFA expression was positively correlated with the levels of pregnenolone (PREG) and E2 in follicles, which also exhibited similar alteration patterns during follicular atresia. ELISA was conducted and indicated for the first time that NORFA induced the synthesis of PREG and E2 in sow GCs in a dose- and time-dependent manner. RNA-seq, GSEA and quantitative analyses results validated that CYP11A1, the coding gene of P450SCC which is the first step rate-limiting enzyme of E2 synthesis, was a positive functional target of NORFA. Mechanistically, NORFA promotes SF-1 expression by stabilizing NR5A1 mRNA through directly interacting with its 3'-UTR, and also tethers SF-1 to shuttle into nucleus. Additionally, SF-1 in the nucleus activates CYP11A1 transcription by directly binding to its promoter, which ultimately induces E2 synthesis and inhibits GC apoptosis., Conclusion: Our findings highlight that NORFA, a multifunctional lncRNA, induces E2 synthesis and inhibits GC apoptosis through the SF-1/CYP11A1 axis in a ceRNA-independent manner, which provide valuable clues and potential targets for follicular atresia inhibition and female fertility improvement., Competing Interests: Declarations Ethics approval and consent to participate All the animal-involved experiments in this study were conducted in accordance with the Chinese guidelines for administration of affairs concerning experimental animals and were reviewed, approved, and supervised by the Institutional Animal Ethics Committee of Nanjing Agricultural University (NJAU.No20220324059). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment., (© 2024. The Author(s).)

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level is challenging due to their less accurate annotation and low expression compared to protein-coding genes. Here, we systematically benchmark different preprocessing methods and develop a computational framework, named ELATUS, based on the combination of the pseudoaligner Kallisto with selective functional filtering. ELATUS enhances the detection of functional lncRNAs from scRNA-seq data, detecting their expression with higher concordance than standard methods with the ATAC-seq profiles in single-cell multiome data. Interestingly, the better results of ELATUS are due to its advanced performance with an inaccurate reference annotation such as that of lncRNAs. We independently confirm the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveil biologically important lncRNAs, such as AL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression is unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs., (© 2024. The Author(s).)

Lung cancer ranks among the most lethal types of cancer globally, with a high occurrence and fatality rate. The spread of cancer to other parts of the body, known as metastasis, is the primary cause of treatment failure and death in lung cancer cases. Current approaches for treating advanced lung cancer typically involve a combination of chemotherapy and targeted therapy. However, the majority of patients ultimately develop resistance to these treatments, leading to a worsened prognosis. In recent years, cancer biology research has predominantly focused on the role of protein-encoding genes in cancer development. Long non-coding RNAs (lncRNAs) are transcripts over 200 nucleotides in length that do not encode proteins but are crucial RNA molecules involved in numerous biological functions. While many functions of lncRNAs remain unknown, some have been linked to human diseases, including cancer. Studies have demonstrated that lncRNAs interact with other large molecules in the cell, such as proteins, DNA, and RNA, influencing various critical aspects of cancer. LncRNAs play a significant role in regulating gene expression and have a crucial function in the transcriptional regulation of cancer cells. They mediate various biological and clinical processes such as invasion, metastasis, apoptosis, and cell proliferation. Dysregulation of lncRNAs has been found to impact the process of carcinogenesis through advanced technologies like RNA sequencing and microarrays. Collectively, these long non-coding RNAs hold promise as potential biomarkers and therapeutic targets for human cancers. In this segment, we provide a comprehensive summary of the literature on the characteristics and formation of lncRNAs, along with an overview of their current known roles in lung cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcoholic liver disease (ALD) is a spectrum of liver damage caused by chronic alcohol consumption. The disease progresses in stages, starting with simple fatty liver, progressing to alcoholic hepatitis and potentially leading to fibrosis and cirrhosis. The pathophysiology of ALD is complex and involves several cellular and molecular mechanisms. Recent research has highlighted the role of long non-coding RNAs (LncRNAs) as critical regulators in the development and progression of ALD. This article reviews the current understanding of LncRNAs in ALD, focusing on their functions in key pathological processes and their potential as diagnostic markers and therapeutic targets., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)