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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.)

Rb/E2f and DREAM complexes play vital roles in regulating cell cycle progression. To date, how they coordinate their functions to regulate cell cycle-dependent gene expression is not clear. Here, we identified a long noncoding RNA (lncRNA), which we named DREAMer , that bridges the interaction between E2f1 and the dREAM complex to regulate endoreplication specifically in Drosophila salivary gland. We show that E2f1 directly stimulates DREAMer expression, whereas DREAMer mediates the repression of e2f1 transcription by modulating the recruitment of the dREAM complex to the e2f1 promoter via a direct interaction with the dREAM component E2f2. The depletion of DREAMer impairs dREAM binding, leading to derepression of e2f1 transcription, which ultimately increases E2f1 activity and promotes the endoreplication. Furthermore, the transcriptomic analysis revealed profound changes in cell cycle-related gene expression in DREAMer KO salivary glands. Together, our findings reveal an lncRNA-mediated link between the dREAM complex and E2f1, which regulates endoreplication during development.

Common variants in the MicroRNA 137 host gene MIR137HG and its adjacent gene DPYD have been associated with schizophrenia risk and the latest Psychiatric Genomics Consortium (PGC). Genome-Wide Association Study on schizophrenia has confirmed and extended these findings. To elucidate the association of schizophrenia risk-associated SNPs in this genomic region, we examined the expression of both mature and immature transcripts of the miR-137 host gene (MIR137HG) in the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) of postmortem brain samples of donors with schizophrenia and psychiatrically-unaffected controls using qPCR and RNA-Seq approaches. No differential expression of miR-137, MIR137HG, or its transcripts was observed. Two schizophrenia risk-associated SNPs identified in the PGC study, rs11165917 (DLPFC: P = 2.0e-16; sgACC: P = 6.4e-10) and rs4274102 (DLPFC: P = 0.036; sgACC: P = 0.002), were associated with expression of the MIR137HG long non-coding RNA transcript MIR137HG-203 (ENST00000602672.2) in individuals of European ancestry. Carriers of the minor (risk) allele of rs11165917 had significantly lower expression of MIR137HG-203 compared with those carrying the major allele. However, we were unable to validate this result by short-read sequencing of RNA extracted from DLPFC or sgACC tissue. This finding suggests that immature transcripts of MIR137HG may contribute to genetic risk for schizophrenia., (Published by Oxford University Press 2024.)

Numerous studies have demonstrated the involvement of messenger RNAs (mRNAs) and non-coding RNAs, including long non-coding RNAs (lncRNA), circular RNAs (circRNAs) and microRNA (miRNAs), in gouty arthritis onset; however, the regulatory mechanism has not yet been elucidated. Here, we applied whole-transcriptome sequencing to identify the differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs between the gout patients and normal people, and constructed co-regulated networks of circRNAs and lncRNAs according to the competitive endogenous RNA (ceRNA) theory for gouty arthritis onset to improve our understanding of the pathogenesis of this disease. The most significant finding of this study is the co-regulated ceRNA network of circRNAs and lncRNAs in gouty arthritis. The circRNA novel&#95;circ&#95;0030384 and the lncRNAs AAMP, TRIM16, PKN1, XLOC&#95;184579 and XLOC&#95;189826 were upstream genes in the co-regulated network. These upstream genes upregulated miR550a-5p and miR550a-3-5p, which downregulated PSME1 and FERMT3 expression. These mRNAs participated in proteasome dynamics, antigen processing and presentation, and platelet activation, which are associated with inflammation in gouty arthritis. In addition, the circRNA and lncRNAs upregulated miR550a-5p, which downregulated GRK2 and OS9 expression. Also, it proved that the down-regulated of PSME1, FERMT3, GRK2 and OS9 can aggravate gouty arthritis in vitro. In summary, these genes mediate inflammation in gouty arthritis through chemokine signaling to regulate neutrophil function., (© 2024. The Author(s).)

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intramuscular fat (IMF) content is an economic trait in beef cattle that improves the meat quality. Studies have highlighted the correlation between long noncoding RNAs (lncRNAs) and IMF development. In this study, lncBNIP3 knockdown promoted bovine intramuscular preadipocyte differentiation. RNA-seq analysis of intramuscular preadipocytes with lncBNIP3 knockdown identified 230 differentially expressed genes. The PI3K-Akt and PPAR signaling pathways were enriched. lncBNIP3 interference promoted mRNA and protein expression of key genes in PI3K-Akt signaling pathway. LncBNIP3 interference reversed the effects of an AKT-inhibitor MK-2206 on Akt protein expression and lipid droplet accumulation, promoted mRNA and protein expression of essential genes in the PPAR signaling pathway, and ameliorated the inhibitory effects of a PPARg antagonist GW9662 on lipid accumulation. Therefore, lncBNIP3 inhibition of bovine intramuscular preadipocyte differentiation is likely mediated via the PI3K-Akt and PPAR signaling pathways. This study identified a valuable lncRNA with functional roles in IMF accumulation and revealed new strategies to improve beef quality.

Infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Understanding the complex interaction between the virus and its host is vital for developing innovative antiviral strategies. Long non-coding RNA (lncRNA) plays a crucial role in regulating host antiviral immune responses. Our previous studies have shown that IBV infection disrupts the stability of lncRNA in host cells, indicating a potential regulatory role for lncRNA in IBV pathogenesis. It is still not clear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection. We demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploring genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100 kb range, we identified chJMJD6 (chicken JMJD6) as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Furthermore, chJMJD6 inhibits STAT1 methylation, thereby affecting the induction of interferon-stimulated genes (ISGs) through the activation of the IFN-β-mediated JAK-STAT signalling pathway, ultimately promoting the intracellular replication of IBV. In summary, our findings reveal the critical role played by lncRNA-DRNR during IBV infection, providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability., (© 2024. The Author(s).)

Disulfidptosis is a novel programmed cell death mode that has been reported to play a role in oncogenesis. Increasing evidences suggest that the long non-coding RNAs (lncRNAs) play crucial roles in the initiation and progression of bladder cancer (BLCA). However, the role and prognostic value of disulfidptosis-related lncRNAs in BLCA remain unknown.The aim of this study was to construct and validate a disulfidptosis-related lncRNA risk model for predicting the prognosis of BLCA patients. A risk model consisting of 5 disulfidptosis-related lncRNAs was developed to predict the prognosis of BLCA patients. The overall survival (OS) of BLCA patients in the high-risk group was significantly shorter than that in the low-risk group (P < 0.05). The effectiveness of this model was validated using the receiver operating characteristic (ROC) curve analysis, and this model proved superior in prognostic accuracy compared with other clinical features. Furthermore, the tumor immune dysfunction and exclusion (TIDE) score in the high-risk group was significantly higher than that in the low-risk group, suggesting that the high-risk group had a less favorable response to immunotherapy. Simultaneously, patients in the low-risk group exhibited significantly higher sensitivity to CTLA-4 monoclonal antibody therapy compared to those in the high-risk group, suggesting potential benefits of immunotherapy for patients in the low-risk group. The combination of high risk and low tumor mutational burden (TMB) could further shortened the OS of BLCA patients. Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients., (© 2024. The Author(s).)

Long noncoding RNAs (lncRNAs) play a significant role in the occurrence and development of malignant tumours. However, ceRNAs, which are significantly associated with the prognosis of breast cancer (BC), need to be further investigated. Therefore, the current study aimed to investigate the effect of the lncRNA DDX11-AS1 on BC progression. Bioinformatics analysis via a public microarray revealed that DDX11-AS1 was upregulated in BC. The above findings were verified via RT‒qPCR analysis of BC tissues. Additionally, our study revealed that the expression levels of DDX11-AS1 increased with increasing pathological grade and lymph node metastasis. Furthermore, DDX11-AS1 knockdown markedly inhibited the proliferation, migration and invasion abilities of BC cells. Mechanistically, DDX11-AS1 could prevent the degradation of MTDH in BC via competitively binding with miR-30c-5p, which could act as a tumour promoter factor. Additionally, miR-30c-5p was downregulated and MTDH was upregulated in BC cells and tissues. The promoting effect of DDX11-AS1 on BC cells was enhanced by miR-30c-5p silencing and reduced by treatment with MTDH inhibitors. Collectively, the above results suggest that the DDX11-AS1/miR-30c-5p/MTDH axis could be associated with the progression of BC and that DDX11-AS1 could be a potential biomarker and therapeutic target for BC., (© 2024. The Author(s).)

Background: This study seeks to elucidate the expressions of lncRNA TSIX in Osteoarthritis (OA) and to explore its mechanisms in regulating OA progression., Methods: RT-qPCR was employed to analyze the expression of TSIX in OA patients classified by Kellgren-Lawrence (K-L) grades. Receiver operator characteristic (ROC) was conducted to evaluate the diagnostic value of TSIX. Correlation between TSIX levels and clinical scores such as Lysholm and visual analogue scale (VAS) score was evaluated using Pearson method. IL-1β-induced SW1353 cells served as an in vitro model. The cell function were assessed by flow cytometry and cell counting kit-8 (CCK-8) assay. The relationship between TSIX and miR-320a was verified by luciferase reporting system, while bioinformatics approaches were utilized to predict the downstream target genes of miR-320a., Results: The findings revealed that TSIX level in OA patients was elevated compared to that of the control group, with a notable progressive increase in TSIX expression correlated with higher K-L grades. In OA patients, the Lysholm score showed a negative correlation with TSIX expression, while the VAS score displayed a positive correlation with TSIX levels. Cell studies demonstrated that inhibition of TSIX enhanced cell viability and mitigated IL-1β-induced apoptosis by targeting miR-320a, in addition to promoting Aggrecan and Collagen II secretion. Luciferase reporter assay further validated the targeting interaction among TSIX, miR-320a, and PTEN., Conclusions: This study demonstrated an increased expression of TSIX in OA patients. It suggests that TSIX may play a role in chondrocyte dysfunction during OA by modulating the miR-320a/PTEN axis., (© 2024. The Author(s).)

Our work aimed to evaluate and differentiate the role of ten lncRNA genes ( GAS5 , HAND2-AS1 , KCNK15-AS1 , MAGI2-AS3 , MEG3 , SEMA3B-AS1 , SNHG6 , SSTR5-AS1 , ZEB1-AS1 , and ZNF667-AS1 ) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues ( p < 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs ( r s < -0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes ( HAND2-AS1 ), peritoneum ( KCNK15-AS1 , MEG3 , and SEMA3B-AS1 ), and greater omentum ( MEG3 , SEMA3B-AS1 , and ZNF667-AS1 ). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent ( p < 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes ( MEG3 , SEMA3B-AS1 , SSTR5-AS1 , ZEB1-AS1 , and ZNF667-AS1 ) in 59 peritoneal metastases. This reversion may be associated with partial epithelial-mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA ( p < 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1 , SSTR5-AS1 , and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC.

The swimming crab ( Portunus trituberculatus ) is an economically important species in China, and its growth traits show obvious sexual dimorphism. Thus, it is important to study the mechanism of sex determination and differentiation in this species. Herein, we identified 2138 differentially expressed genes and 132 differentially expressed long non-coding RNAs (lncRNAs) using Oxford Nanopore Technology full-length transcriptome sequencing. We predicted 561 target genes of the differentially expressed lncRNAs according to their location and base pair complimentary principles. Furthermore, pathways related to sex determination, differentiation, and reproduction were enriched for lncRNAs according to gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. This indicated that lncRNAs might play regulatory roles in these pathways. Our results could form the basis for future studies of sex determination and differentiation in P. trituberculatus .

Background: Chickens play a crucial role as the primary global source of eggs and poultry, and the quality of rooster semen significantly impacts poultry reproductive efficiency. Therefore, it is imperative to comprehend the regulatory mechanisms underlying sperm development., Results: In this study, we established transcriptome profiles of lncRNAs, miRNAs, and mRNAs in 3 testis tissues and 3 epididymis tissues from "Jing Hong No.1" roosters at 24, 35, and 64 weeks of age. Using the data, we conducted whole transcriptome analysis and constructed a ceRNA network. We detected 10 differentially expressed mRNAs (DEmRNAs), 33 differentially expressed lncRNAs (DElncRNAs), and 10 differentially expressed miRNAs (DEmiRNAs) in the testis, as well as 149 DEmRNAs, 12 DElncRNAs, and 10 DEmiRNAs in the epididymis. These genes were found to be involved in cell differentiation and development, as well as various signaling pathways such as GnRH, MAPK, TGF-β, mTOR, VEGF, and calcium ion pathways. Subsequently, we constructed two competing endogenous RNA (ceRNA) networks comprising DEmRNAs, DElncRNAs, and DEmiRNAs. Furthermore, we identified four crucial lncRNA-mRNA-miRNA interactions that govern specific biological processes in the chicken reproductive system: MSTRG.2423.1-gga-miR-1563-PPP3CA and MSTRG.10064.2-gga-miR-32-5p-GPR12 regulating sperm motility in the testis; MSTRG.152556.1-gga-miR-9-3p-GREM1/THYN1 governing immunomodulation in the epididymis; and MSTRG.124708.1-gga-miR-375-NDUFB9/YBX1 controlling epididymal sperm maturation and motility., Conclusions: Whole transcriptome sequencing of chicken testis and epididymis screened several key genes and ceRNA regulatory networks, which may be involved in the regulation of epididymal immunity, spermatogenesis and sperm viability through the pathways of MAPK, TGF-β, mTOR, and calcium ion. These findings contribute to our comprehensive understanding of the intricate molecular processes underlying rooster spermatogenesis, maturation and motility., (© 2024. The Author(s).)

In plants, sugars are the key source of energy and metabolic building blocks. The systemic transport of sugars is essential for plant growth and morphogenesis. Plants evolved intricate molecular networks to effectively distribute sugars. The dynamic distribution of these osmotically active compounds is a handy tool for regulating cell turgor pressure, an instructive force in developmental biology. In this study, we have investigated the molecular mechanism behind the dual role of the receptor-like kinase CANAR. We functionally characterized a long non-coding RNA, CARMA, as a negative regulator of CANAR. Sugar-responsive CARMA specifically fine-tunes CANAR expression in the phloem, the route of sugar transport. Our genetic, molecular, microscopy, and biophysical data suggest that the CARMA-CANAR module controls the shoot-to-root phloem transport of sugars, allows cells to flexibly adapt to the external osmolality by appropriate water uptake, and thus adjust the size of vascular cell types during organ growth and development. Our study identifies a nexus of plant vascular tissue formation with cell internal pressure monitoring, revealing a novel functional aspect of long non-coding RNAs in developmental biology., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

The persistence of cancer stem cells (CSC) is believed to contribute to resistance to platinum-based chemotherapy and disease relapse in ovarian cancer, the fifth leading cause of cancer-related death among US women. HOXC transcript antisense RNA (HOTAIR) is a long, noncoding RNA (lncRNA) overexpressed in high-grade serous ovarian cancer and linked to chemoresistance. However, HOTAIR impacts chromatin dynamics in ovarian CSCs. Oncogenic lncRNA's contributions to drug-resistant disease are incompletely understood. Here, we generated HOTAIR knockout (KO) high-grade serous ovarian cancer cell lines using paired CRISPR guide RNA design to investigate the function of HOTAIR. We show the loss of HOTAIR function resensitized ovarian cancer cells to platinum treatment and decreased the population of ovarian CSCs. Furthermore, HOTAIR KO inhibited the development of stemness-related phenotypes, including spheroid formation ability and expression of key stemness-associated genes ALDH1A1, NOTCH3, SOX9, and PROM1. HOTAIR KO altered the cellular transcriptome and chromatin accessibility landscape of multiple oncogenic-associated genes and pathways, including the NF-kB pathway. HOTAIR functions as an oncogene by recruiting enhancer of zeste homolog 2 (EZH2) to catalyze H3K27 trimethylation to suppress downstream tumor suppressor genes, and it was of interest to inhibit both HOTAIR and EZH2. In vivo, combining a HOTAIR inhibitor with an EZH2 inhibitor and platinum chemotherapy decreased tumor formation and increased survival. These results suggest a key role for HOTAIR in ovarian CSCs and malignant potential. Targeting HOTAIR in combination with epigenetic therapies may represent a therapeutic strategy to ameliorate ovarian cancer progression and resistance to platinum-based chemotherapy., (©2024 American Association for Cancer Research.)

Progression of diabetic retinopathy resists arrest even after institution of intensive glycemic control, suggesting a "metabolic memory" phenomenon, but the mechanism responsible for this phenomenon is still elusive. Gene expression and biological processes can also be regulated by long noncoding RNAs (LncRNAs), the RNAs with >200 nucleotides and no open reading frame for translation, and several LncRNAs are aberrantly expressed in diabetes. Our aim was to identify retinal LncRNAs that fail to reverse after termination of hyperglycemia. Microarray analysis was performed on retinal RNA from streptozotocin-induced diabetic rats in poor glycemic control for 8 months, followed by in good glycemic control (blood glucose >400 mg/dL), or for 4 months, with four additional months of good glycemic control (blood glucose <150 mg/dL). Differentially expressed LncRNAs and mRNAs were identified through Volcano filtering, and their functions were predicted using gene ontology and pathway enrichment analyses. Compared with age-matched normal rats, rats in continuous poor glycemic control had >1479 differentially expressed LncRNAs (710 downregulated, 769 upregulated), and among those, 511 common LncRNAs had similar expression in Diab and Rev groups (139 downregulated, 372 upregulated). Gene Ontology/pathway analysis identified limited LncRNAs in biological processes, but analysis based on biological processes/molecular function revealed >350 genes with similar expression in Diab and Rev groups; these genes were mainly associated with stress response, cell death, mitochondrial damage and cytokine production. Thus, identifying retinal LncRNAs and their gene targets that do not benefit from termination of hyperglycemia have potential to serve as therapeutic targets to slow down the progression of diabetic retinopathy., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Long noncoding RNAs (lncRNAs) are involved in the regulation of triple-negative breast cancer (TNBC) senescence, while pro-carcinogenic lncRNAs resist senescence onset leading to the failure of therapy-induced senescence (TIS) strategy, urgently identifying the key senescence-related lncRNAs (SRlncRNAs). We mined seven SRlncRNAs (SOX9-AS1, LINC01152, AC005152.3, RP11-161 M6.2, RP5-968 J1.1, RP11-351 J23.1 and RP11-666A20.3) by bioinformatics, of which SOX9-AS1 was reported to be pro-carcinogenic. In vitro experiments revealed the highest expression of SOX9-AS1 in MDA-MD-231 cells. SOX9-AS1 knockdown inhibited cell growth (proliferation, cycle and apoptosis) and malignant phenotypes (migration and invasion), while SOX9-AS1 overexpression rescued these effects. Additionally, SOX9-AS1 knockdown facilitated tamoxifen-induced cellular senescence and the transcription of senescence-associated secretory phenotype (SASP) factors (IL-1α, IL-1β, IL-6 and IL-8) mechanistically by resisting senescence-induced Wnt signal (GSK-3β/β-catenin) activation. Immune infiltration analysis revealed that low SOX9-AS1 expression was accompanied by a high infiltration of naïve B cells, CD8 + T cells and γδ T cells. In conclusion, SOX9-AS1 resists TNBC senescence via regulating the Wnt signalling pathway and inhibits immune infiltration. Targeted inhibition of SOX9-AS1 enhances SASP and thus mobilises immune infiltration to adjunct TIS strategy., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Respiratory diseases in children are common health problems that significantly impact their quality of life and health status, and this has its own unique challenges compared to adults. A growing body of research has focused on epigenetic mechanisms that relate with the development of various diseases, such as pediatric respiratory diseases. Noncoding RNAs (ncRNAs), especially long noncoding RNAs, microRNA, and circular RNA, are reported to play a regulatory role in pediatric respiratory diseases whose mutations or aberrant expressions are strongly associated with the development of these diseases. In this review, we mainly discussed the functions of these three ncRNAs in pediatric respiratory diseases.

Increasing evidence demonstrate that the significant role of long non-coding RNA (lncRNA) in metastasis and the remodeling of the tumor microenvironment. However, the precise mechanisms of lncRNAs in cancer metastasis are still poorly understood. The function of lncRNA-Mir100hg in melanoma and its involvement in mediating communication between tumor stem cells and non-stemness tumor cells remains unknown. We found that Mir100hg is upregulated in melanoma stem cells (CSCs) known as OLSD. Furthermore, Mir100hg can be transferred from OLSD to non-stem cancer cells (OL) through exosomes. Once Mir100hg enters OL cells, it operates through a competitive endogenous RNA (ceRNA) mechanism. It competes with microRNAs (miR-16-5p and miR-23a-3p) by binding to them, thus preventing these miRNAs from targeting their mRNAs. As a result, the expression of glycolysis-related mRNA was restored. This ultimately enhances the metastatic capability of OL cells. In summary, our study uncovers a network used by CSCs to transfer their high metastatic activity to non-stem cancer cells through the exosomal Mir100hg. This mechanism sheds new light on the communication between heterogeneous cancer cell populations in melanoma. Importantly, it provides novel insights into the role of lncRNAs in cancer metastasis and highlights the significance of the tumor microenvironment in facilitating metastasis., 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.)

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer 1,2 . Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA. We reveal a pattern highly indicative of tissue-context-based selection for ecDNAs, linking their genomic content to their tissue of origin. We show that not only is ecDNA a mechanism for amplification of driver oncogenes, but it also a mechanism that frequently amplifies immunomodulatory and inflammatory genes, such as those that modulate lymphocyte-mediated immunity and immune effector processes. Moreover, ecDNAs carrying immunomodulatory genes are associated with reduced tumour T cell infiltration. We identify ecDNAs bearing only enhancers, promoters and lncRNA elements, suggesting the combinatorial power of interactions between ecDNAs in trans. We also identify intrinsic and environmental mutational processes linked to ecDNA, including those linked to its formation, such as tobacco exposure, and progression, such as homologous recombination repair deficiency. Clinically, ecDNA detection was associated with tumour stage, more prevalent after targeted therapy and cytotoxic treatments, and associated with metastases and shorter overall survival. These results shed light on why ecDNA is a substantial clinical problem that can cooperatively drive tumour growth signals, alter transcriptional landscapes and suppress the immune system., (© 2024. The Author(s).)

Aim: To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI)., Methods: Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR-124-3p, which were then validated through a dual-luciferase assay. Following transfection, the relationships between Malat1, miR-124-3p, and Lamc1 expression levels were assessed by qRT-PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin-eosin (HE) staining. Basso-Beattie-Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway-related protein., Results: Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR-124-3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR-124-3p reversed the silencing effects of Malat1., Conclusions: Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR-124-3p, thereby regulating As activity to repair SCI., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Long noncoding (Lnc) RNAs are novel regulators in melanoma. Lnc nuclear enriched autosomal transcript 1 (NEAT1) was reportedly upregulated in melanoma; however, the functional roles and mechanisms of Lnc NEAT1 need further investigation. Therefore, we used quantitative real-time PCR to determine the mRNA levels of Lnc NEAT1, miR-152-3p, and cyclin-dependent protein kinase 6 (CDK6). The protein level of CDK6 was determined by Western blot. Cell counting kit 8 and colony formation assays were used to assess cell proliferation. Cell migration was measured by wound healing and Transwell assays. Direct binding of the indicated molecules was verified by an RNA-binding protein immunoprecipitation assay and a dual luciferase reporter assay. The results revealed that Lnc NEAT1 and CDK6 were elevated, while miR-152-3p was downregulated in melanoma. Furthermore, Lnc NEAT1 was positively correlated with CDK6 expression and negatively correlated with miR-152-3p level. Furthermore, Lnc NEAT1 facilitated proliferation, migration, and invasion of melanoma cells. The underlying mechanism is that Lnc NEAT1 serves as a sponge for miR-152-3p to suppress the inhibitory effect of miR-152-3p on CDK6. Furthermore, the miR-152-3p/ CDK6 axis was implicated in the progression of melanoma accelerated by Lnc NEAT1. Taken together, Lnc NEAT1 may promote melanoma development by serving as an endogenous sponge of miR-152-3p, increasing CDK6 expression, and identifying a new target for the treatment of melanoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Parkinson's disease (PD) is a prevalent type of neurodegenerative disorder. AVE0991, a non-peptide analogue of Ang-(1-7), by which the progression of PD has been discovered to be ameliorated, but the specific mechanism whereby AVE0991 modulates the progression of PD re-mains unclear. The mice overexpressing human α-syn (A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing hα-syn (A53T). The [ 18 F] FDG-PET/CT method was employed to assess FDG uptake in human α-syn (A53T) overexpressing mice. Levels of lnc HOTAIRM1 and miR-223-3p were detected via qRT-PCR. Flow cytometry was deployed to assay cell apoptosis. Here, we found that AVE0991 improved behaviour disorders and decreased α-syn expression in the substantia nigra of mice with Parkinson's disease. AVE0991 inhibited the apoptosis of dopaminergic neurons overexpressing hα-syn (A53T) via lncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Moreover, miR-223-3p level in peripheral blood was found negatively correlated with the α-syn. Our present study shows that the angiotensin-(1-7) analogue AVE0991 targeted at the HOTAIRM1/miR-223-3p axis to degrade α-synuclein in PD mice, and showed neuroprotection in vitro., (© 2024. The Author(s).)

Background: Sepsis-induced myocardial injury (SIMI) is a severe complication of sepsis, contributing significantly to mortality. Mitochondrial dysfunction and dysregulated autophagy are implicated in SIMI pathogenesis. Long non-coding RNA MALAT1 has been associated with various diseases, including sepsis, but its role in SIMI remains unclear., Objective: This study aimed to investigate the role of lncRNA MALAT1 in SIMI, specifically in the regulation of mitochondrial autophagy., Methods: A sepsis-induced cardiomyopathy model was established in mice, and the cardiac tissues were analyzed. The expression of lncRNA MALAT1 was modulated and its effects on mitochondrial autophagy, myocardial injury, inflammation, and apoptosis were assessed. Furthermore, the interaction between MALAT1 and miR-146a was explored, as well as the involvement of the TLR4/NF-kB/MAPK signaling pathway., Results: Activation of mitochondrial autophagy by urolithin A (UA) alleviated SIMI, inflammation, and cardiac dysfunction. Downregulation of MALAT1 enhanced mitochondrial autophagy, stabilized the mitochondrial membrane potential, and inhibited mitochondrial reactive oxygen species (ROS) production, leading to improved cell viability and reduced myocardial injury. Furthermore, MALAT1 interacted with miR-146a, and their modulation influenced mitochondrial autophagy, myocardial injury, and inflammation. The TLR4/NF-kB/MAPK signaling pathway was implicated in these processes., Conclusion: Our findings suggest that lncRNA MALAT1 plays a crucial role in SIMI by modulating miR-146a-mediated mitochondrial autophagy and the TLR4/NF-kB/MAPK signaling pathway. These results provide new insights into the pathogenesis of SIMI and potential therapeutic targets., (© 2024. The Author(s).)

Deep second- or mixed-degree burn lesions are difficult to heal due to the impaired dermis supporting of epidermis renewal and nutrition delivery. Early dermis debridement and preservation speed healing and enhance results, emphasizing the need of knowing processes that promote burn-denatured dermis recovery, notably endothelial cell angiogenesis and autophagy. Integrative bioinformatics investigations identified AGAP2-AS1 as a highly elevated lncRNA in burn tissues. Pearson's correlation study connected AGAP2-AS1 to 112 differently co-expressed protein-coding genes involved in burn healing processes such cell cycle and TGF-beta receptor signaling. Experimental validation showed that heat damage elevated AGAP2-AS1 in HUVECs and HDMECs. Functionally, AGAP2-AS1 overexpression in heat-denatured HUVECs and HDMECs increased cell survival, migration, invasion, and angiogenesis. In addition, AGAP2-AS1 overexpression increased endothelial cell autophagy. Additional investigation showed AGAP2-AS1's association with ATG9A, stabilizing it. Post-heat damage, ATG9A knockdown drastically reduced HUVEC and HDMEC survival, migration, invasion, angiogenesis, and autophagy. More notably, ATG9A knockdown drastically reduced the benefits of AGAP2-AS1 overexpression on endothelial cell functions and autophagy. The positive association between AGAP2-AS1 and ATG9A expression in burn tissue samples highlights their crucial roles in endothelial cell response to heat injury, indicating that targeting this axis may aid burn wound healing. The research found that lncRNA AGAP2-AS1 stabilizes ATG9A and promotes autophagy in endothelial cells. These results imply that targeting the AGAP2-AS1/ATG9A axis may improve angiogenesis and tissue regeneration in burn injuries, revealing burn wound healing molecular pathways., 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 Inc.)

Bipolar disorder (BD) is a psychiatric condition that is frequently misdiagnosed and linked to inadequate treatment. Long non-coding RNAs (lncRNAs) have lately gained recognition as crucial genetic elements and are now regarded as regulatory mechanisms in the neurological system. Our objective was to measure the quantities of HOXA-AS2 and MEG3 ncRNA transcripts. HOXA-AS2 and MEG3 ncRNA levels were checked in the peripheral blood of 50 type I BD and 50 control samples by real-time PCR. Furthermore, we conducted ROC curve analysis and correlation analysis to examine the association between gene expression and specific clinical characteristics in instances with BD. Additionally, a computational study was performed to investigate the binding sites of miRNAs on the HOXA-AS2 and MEG3 lncRNAs. BD subjects showed a significant increase in the expression of HOXA-AS2 and MEG3 compared to controls. The lncRNAs HOXA-AS2 and MEG3 have an area under the ROC curve (AUC) values of 0.70 and 0.71, respectively. There was a significant correlation between the expression levels of ncRNAs HOXA-AS2 and MEG3 in the peripheral blood of patients with BD and occupation scores. The data presented indicate a potential correlation between the expression of HOXA-AS2 and MEG3 lncRNAs with an elevated risk of BD. Furthermore, these lncRNAs may be linked to several molecular pathways. Our findings indicate that the amounts of lncRNAs HOXA-AS2 and MEG3 in transcripts might be a promising potential biomarker for patients with BD., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Tumor cell invasion is considered as one of the main therapeutic challenges in cancer patients, which leads to distant metastasis and reduced prognosis. Therefore, investigation of the factors involved in tumor cell invasion improves the therapeutic methods to reduce tumor metastasis. Epithelial-mesenchymal transition (EMT) process has a pivotal role in tumor cell invasion and metastasis, during which tumor cells gain the invasive ability by losing epithelial characteristics and acquiring mesenchymal characteristics. WNT/β-catenin signaling pathway has a key role in tumor cell invasion by regulation of EMT process. Long non-coding RNAs (lncRNAs) have also an important role in EMT process through the regulation of WNT/β-catenin pathway. Deregulation of lncRNAs is associated with tumor metastasis in different tumor types. Therefore, in the present review, we investigated the role of lncRNAs in EMT process and tumor cell invasion through the regulation of WNT/β-catenin pathway. It has been reported that lncRNAs mainly induced the EMT process and tumor cell invasion through the activation of WNT/β-catenin pathway. LncRNAs that regulate the WNT/β-catenin mediated EMT process can be introduced as the prognostic markers as well as suitable therapeutic targets to reduce the tumor metastasis in cancer patients., 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 GmbH. All rights reserved.)

Background/aim: Certain long non-coding RNAs (lncRNAs), identified as potential tumor suppressors, have shown potential in inhibiting tumor growth. Here, we investigated a novel mechanism involving the direct interaction between lncRNA TPRG1-AS1 and Clathrin Heavy Chain (CLTC) in the Epidermal Growth Factor (EGF) signaling pathway for its tumor-suppressive effects., Materials and Methods: Our research revealed a direct physical interaction between TPRG1-AS1 and CLTC through RNA pulldown and RNA immunoprecipitation (RIP)-qPCR, which subsequently influenced the EGF signaling pathway. We confirmed phenotype changes by cell viability, sphere formation, and invasion. We confirmed the mechanism underlying these phenotypic changes through immunoblotting and immunocytochemistry., Results: Firstly, we confirmed a reduction in the phenotype associated with the overexpression of TPRG1-AS1 (TPRG1-AS1oe) interacting with CLTC in the presence of EGF signaling. Next, it was observed that TPRG1-AS1oe suppressed EGF downstream signaling, specifically MAPK8 and MAPK14, in relation to CLTC. Moreover, we verified that overexpressed TPRG1-AS1 binds to CLTC and suppresses EGF downstream signaling using a custom HEX probe., Conclusion: Collectively our study uncovered a novel regulatory axis wherein TPRG1-AS1 interacts with CLTC, consequently attenuating EGF downstream signaling, particularly through the MAPK8 and MAPK14 pathways. These complex interactions ultimately lead to a reduction in the phenotype of liver cancer cells., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

RNA molecules form complex networks of molecular interactions that are central to their function and to cellular architecture. But these interaction networks are difficult to probe in situ. Here, we introduce Oligonucleotide-mediated proximity-interactome MAPping (O-MAP), a method for elucidating the biomolecules near an RNA of interest, within its native context. O-MAP uses RNA-fluorescence in situ hybridization-like oligonucleotide probes to deliver proximity-biotinylating enzymes to a target RNA in situ, enabling nearby molecules to be enriched by streptavidin pulldown. This induces exceptionally precise biotinylation that can be easily optimized and ported to new targets or sample types. Using the noncoding RNAs 47S, 7SK and Xist as models, we develop O-MAP workflows for discovering RNA-proximal proteins, transcripts and genomic loci, yielding a multiomic characterization of these RNAs' subcellular compartments and new regulatory interactions. O-MAP requires no genetic manipulation, uses exclusively off-the-shelf parts and requires orders of magnitude fewer cells than established methods, making it accessible to most laboratories., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background/aim: Glioma, the most common type of primary brain tumor, is characterized by high malignancy, recurrence, and mortality. Long non-coding RNA (lncRNA) H19 is a potential biomarker for glioma diagnosis and treatment due to its overexpression in human glioma tissues and its involvement in cell division and metastasis regulation. This study aimed to identify potential therapeutic targets involved in glioma development by analyzing gene expression profiles regulated by H19., Materials and Methods: To elucidate the role of H19 in A172 and U87MG glioma cell lines, cell counting, colony formation, and wound healing assays were conducted. RNA-seq data analysis and bioinformatics analyses were performed to reveal the molecular interactions of H19., Results: Cell-based experiments showed that elevated H19 levels were related to cancer cell survival, proliferation, and migration. Bioinformatics analyses identified 2,084 differentially expressed genes (DEGs) influenced by H19 which are involved in cancer progression. Specifically, ANXA5, CLEC18B, RAB42, CXCL8, OASL, USP18, and CDCP1 were positively correlated with H19 expression, while CSDC2 and FOXO4 were negatively correlated. These DEGs were predicted to function as oncogenes or tumor suppressors in gliomas, in association with H19., Conclusion: These findings highlight H19 and its associated genes as potential diagnostic and therapeutic targets for gliomas, emphasizing their clinical significance in patient survival., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Neuroblastoma (NB), the most common extracranial solid tumor in pediatric patients, manifests with considerable variability across multiple primary sites. Despite this, the extent of genetic heterogeneity within these tumor foci and the identification of consistent oncogenic drivers remains largely unexplored. Of particular interest, genetic mutations in PHOX2B have been linked to familial cases of NB, yet the underlying molecular mechanisms are not fully delineated. In our research, we focus on unraveling the role of a novel functional long non-coding RNA (lncRNA) associated with PHOX2B in the context of NB. Using NB cell models with overexpressed PHOX2B, combined with lncRNA microarray analysis, we discovered that lncARSR is significantly upregulated in response to PHOX2B overexpression. Subsequent biological assays demonstrated that lncARSR promotes both the proliferation and metastasis of NB cells. Further molecular investigations revealed that lncARSR plays a crucial role in stabilizing PHOX2B expression within NB cells. Moreover, we identified that the expression of lncARSR is regulated by methylation through methyltransferase-like 3 (METTL3), which itself is positively correlated with PHOX2B expression. Rescue experiments underscored the functional importance of METTL3, lncARSR, and PHOX2B in NB cells. In summary, our findings provide new insights into the molecular functions of PHOX2B in the progression of neuroblastoma and propose a novel therapeutic target for this aggressive malignancy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Non-coding RNAs (lncRNAs) play critical roles in various cellular processes, including a novel form of regulated cell death known as disulfidptosis, characterized by accumulating protein disulfide bonds and severe endoplasmic reticulum stress. This review highlights the therapeutic potential of lncRNAs in regulating disulfidptosis for cancer treatment, emphasizing their influence on key pathway components such as GPX4, SLC7A11, and PDIA family members. Recent studies have demonstrated that targeting specific lncRNAs can sensitize cancer cells to disulfidptosis, offering a promising approach to cancer therapy. The regulation of disulfidptosis by lncRNAs involves various signaling pathways, including oxidative stress, ER stress, and calcium signaling. This review also discusses the molecular mechanisms underlying lncRNA regulation of disulfidptosis, the challenges of developing lncRNA-based therapies, and the future potential of this rapidly advancing field in cancer research., 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 GmbH. All rights reserved.)

Gastric cancer (GC) is a malignancy with a relatively high mortality rate. This study aimed to ascertain the prognostic significance of long non-coding RNA (lncRNA) AC010457.1 in GC and elucidate its role in disease progression. The Cancer Genome Atlas (TCGA) database was used to screen the prognosis-associated differentially expressed lncRNAs in GC patients. Kaplan-Meier curves, univariate and multivariate Cox regression analyses were applied to assess the prognostic significance of AC010457.1. In vitro and in vivo functional assays were performed to evaluate the effects of AC010457.1 on cellular proliferation and metastasis. Mechanistic investigations, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Western blotting (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), were used to explore the signaling pathways activated by AC010457.1. We demonstrated that AC010457.1 was abnormally upregulated in GC tissues, and that this aberrant upregulation was associated with a poor prognosis for GC patients. The functional experiments proved that the downregulated of AC010457.1 hindered GC cell proliferation, migration, and invasive potential. Furthermore, KEGG analysis revealed a significant association between AC010457.1 and the PI3K/AKT signaling pathway, which was further corroborated by WB analysis. Rescue experiments provided additional confirmation that AC010457.1 regulated PI3K/AKT promote GC proliferation, migration, and epithelial-mesenchymal transition (EMT). Collectively, our findings suggest that AC010457.1 overexpression serves as a distinct prognostic risk factor in GC and may represent a promising therapeutic target for the treatment of this malignancy., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is an epithelial carcinoma arising from the nasopharyngeal mucosal lining. The present study sought to analyze the mechanism by which homeobox A10 (HOXA10) affects NPC cell proliferation. The expression levels of HOXA10/long noncoding RNA (lncRNA) PTPRG antisense RNA 1 (PTPRG-AS1)/ubiquitin-specific peptidase 1 (USP1) in NPC tissues and cells were determined. Cell proliferation was evaluated. The enrichment of HOXA10 on the PTPRG-AS1 promoter was determined. The binding of PTPRG-AS1, HuR, and USP1 to each other was analyzed via RNA immunoprecipitation. USP1 mRNA stability was determined after actinomycin D treatment. The role of the PTPRG-AS1/USP1 axis in NPC cell proliferation was analyzed in combined experiments. The role of HOXA10 in vivo was confirmed in xenograft tumor models. The results revealed that HOXA10 was overexpressed in NPC. HOXA10 downregulation reduced NPC cell proliferation. PTPRG-AS1 and USP1 were upregulated in NPC. HOXA10 bound to the PTPRG-AS1 promoter to increase PTPRG-AS1 expression, and the binding of PTPRG-AS1 to HuR increased USP1 expression. PTPRG-AS1 or USP1 overexpression attenuated the inhibitory effects of HOXA10 downregulation on NPC cell proliferation. HOXA10 downregulation inhibited in vivo NPC proliferation through the PTPRG-AS1/USP1 axis. In conclusion, HOXA10 facilitates NPC cell proliferation in vitro and in vivo through the PTPRG-AS1/USP1 axis., (© 2024 Wiley Periodicals LLC.)

Colorectal cancer (CRC) represents a substantial challenge to public health. Despite extensive research, the pathogenesis of CRC is not yet fully elucidated, hindering the development of effective therapeutic strategies. Recent advancements have underscored the importance of Non-coding RNAs in tumor biology. Our research identified a significant upregulation of Linc00475 in CRC, which correlated with reduced survival rates among CRC patients. Consequently, this study aimed to elucidate the mechanisms by which Linc00475 contributed to CRC progression. Employing a comprehensive array of experimental techniques-including CCK-8 assays, colony formation assays, flow cytometry, quantitative PCR (qPCR), western blot analysis, and in vivo tumorigenesis assays-we have demonstrated that Linc00475 enhances CRC cell proliferation. Further analysis revealed that Linc00475 directly interacted with miR-107, leading to its downregulation. Moreover, our findings confirmed that miR-107 directly targeted CDK6, which was markedly downregulated following Linc00475 silencing. In vivo experiments further indicated that the silencing of Linc00475 markedly inhibited the proliferation of CRC cells. Collectively, our findings suggested that Linc00475 facilitated CRC cell proliferation through the regulation of the miR-107/CDK6 axis, thereby providing a novel perspective for understanding the molecular mechanisms underlying CRC development., (© 2024 Wiley Periodicals LLC.)