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Background and objectives: Parkinson's disease (PD) is a common neurodegenerative disorder with unclear molecular mechanisms. Noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been identified as critical regulators of gene expression. This study aimed to investigate the triple network of lncRNA-miRNA-mRNA, known as competing endogenous RNAs (ceRNAs), and to identify essential lncRNAs that regulate PD-related gene expression through their target miRNAs. The study also identified a common triple network between COVID-19 and PD that may contribute to exacerbating PD symptoms. Methods: A bioinformatics approach was employed to construct a PD ceRNA network using common PD genes, miRNAs and lncRNAs with the highest interaction with their targets. Also, a PD-COVID-19 triple network was constructed by integrating PD network nodes into the COVID-19 network. Results: The PD ceRNA network comprised 34 nodes, including 12 lncRNAs, 16 miRNAs with interconnections and six mRNAs, some of which were related to COVID-19. The network showed parallel expression of the SNCA and PARK7 genes as well as the NEAT1 and MALAT1 lncRNAs in both PD and COVID-19. Conclusions: This study provide insights into the molecular mechanisms underlying the worsening of symptoms in PD patients with COVID-19. The PD and COVID-19 ceRNA network indicates that coronavirus could worsen PD symptoms by altering the expression of some genes related to PD. Therefore, COVID-19 could dysregulate the common RNAs involved in PD through lncRNAs, miRNAs. [ABSTRACT FROM AUTHOR]

In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR (p53 Inactivating TRIM28 Associated RNA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR, in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28-dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR, which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target.

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor β-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase β (CaMKKβ), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.

Background: Previous studies have shown that necroptosis-related long noncoding RNA (lncRNA) risk models can be used to predict prognosis and immune infiltration in patients with esophageal cancer. However, further analysis of the regulatory mechanisms of necroptosis-related lncRNAs used in risk models remains to be conducted. The purpose of the present study was to identify valuable necroptosis-related lncRNAs in esophageal cancer and to verify their molecular and cellular functions. Methods: Esophageal cancer data were downloaded from The Cancer Genome Atlas (TCGA). The expression of eight genes (LINC00299, AC090912.2, AC244197.2, AL158166.1, AC079684.1, AP003696.1, AC079684.1 and AP003696.1) in the necroptosis-related lncRNA risk model, their relationships with clinicopathological stage, and their diagnostic receiver operating characteristic (ROC) curves were analyzed. The prognostic value of these lncRNAs for overall survival (OS) and disease specific survival (DSS) was analyzed, and time-dependent ROC curves were generated. The AP003696.1 target gene (lncRNA ENSG00000253385.1) was further investigated through immune infiltration analysis, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analyses, and gene coexpression analysis. Finally, in vitro functional assays based on lncRNA ENSG00000253385.1 were conducted to explore its regulatory role in esophageal cancer. Results: A bioinformatics approach was used to study the eight genes in the necroptosis-related lncRNA risk model. AP003696.1 (lncRNA ENSG00000253385.1) was highly expressed in esophageal cancer tissues, and its high expression was correlated with poor OS and DFdS. Both univariate and multivariate Cox regression analyses revealed that lncRNA ENSG00000253385.1 is an independent prognostic factor. The lncRNA ENSG00000253385.1 gene was demonstrated to play a definite role in the invasion of esophageal cancer immune cells and in signaling pathways in these cells. In vitro cell functional assays revealed that lncRNA ENSG00000253385.1 expression was elevated in the KYSE150 and KYSE410 esophageal cancer cell lines. Small interfering RNA (siRNA)-mediated silencing of lncRNA ENSG00000253385.1 significantly inhibited the proliferation, migration, and invasion of KYSE150 and KYSE410 cells, as well as promoted their apoptosis. Conclusions: The ENSG00000253385.1 gene may be a key gene in the occurrence, development, and prognosis of esophageal cancer. These findings provide new ideas and references for the screening of therapeutic targets, as well as the development of targeted drugs, for esophageal cancer treatment.

Abstract Long non‐coding RNA RP11‐64B16.4 (myocardial infarction protection‐related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re‐expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta‐8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL‐mediated anti‐apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia‐enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Abstract Disulfidptosis, a new type of regulated cell death associated with the actin cytoskeleton, provides a new therapeutic tool for cancers. The direct relationship between disulfidptosis-related lncRNAs(DRLs) in liver hepatocellular carcinoma(HCC) remains unclear. We acquired transcriptomic data, corresponding clinical data, and tumor mutation data of HCC from the TCGA database. First of all, DRLs were determined through correlation analysis. Then, a prognostic model containing six DRLs was created by adopting univariate Cox regression, LASSO algorithm and multivariate Cox regression analysis. Based on the model, 424 HCC patients were divided into high- and low-risk groups. Next, we structured ROC curves and PCA through combining the model and clinical data. Enrichment analysis and immune infiltration analysis were adopted to further explore the relationship between the model and prognosis. In addition, we explored the relationship between the model and tumor mutation burden (TMB). There were significant differences between high- and low- risk groups, and patients in the high-risk group showed poor prognosis. Enrichment analysis suggested that metabolic progress was obviously different between the two groups. According to the analysis of immune infiltration, there were several differences in immune cells, function, and checkpoints. Patients with high-risk and high TMB demonstrated the least favorable prognosis. The two risk groups both manifested visiblly in chemotherapy drug sensitivity. To sum up, we set up a DRL-based signature and that may provide a predictable value for the prognosis and use of chemotherapy drugs for HCC patients.

Abstract Purpose Disulfidptosis, a newly identified form of cell death, is triggered by disulfide stress. Herein, a unique signature was developed based on disulfidptosis-related lncRNAs (DRlncRNAs) for the prognostic and immune landscape prediction of head and neck squamous cell carcinoma (HNSCC). Methods Transcriptome, somatic mutation, and clinical data were acquired at The Cancer Genome Atlas database. Individuals were partitioned into training and test cohorts at a 1:1 ratio to facilitate the development of a DRlncRNA signature using the least absolute shrinkage and selection operation method. Based on the median risk score, all HNSCC individuals were stratified into the high-risk group (HRG) and low-risk group (LRG). Kaplan–Meier survival and time-dependent receiver operating characteristic (ROC) analyses were used to estimate the prognostic value, and a nomogram was generated for survival prediction. To provide a more comprehensive assessment, the tumor microenvironment, functional enrichment, immune cell infiltration, and immunotherapeutic sensitivity were explored between LRG and HRG. Results A DRlncRNA signature was established with 10 DRlncRNAs. The corresponding values of areas under the ROC curves for 1–, 3–, and 5–year overall survival were 0.710, 0.692, and 0.640. A more favorable prognosis was noted in the patients with lower risk, along with higher immune scores, increased immune-related functions, and immune cell infiltration, as well as improved response to the immunotherapeutic intervention in comparison with individuals at higher risk. Conclusion These findings demonstrate that the developed DRlncRNA signature holds promise as a reliable prognostic marker and predictor of immunotherapy response in HNSCC patients.

Abstract Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs.

Abstract Background Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI. Methods Since expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples. Results We showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR. Conclusion Our data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.

Abstract Objective In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified. Methods In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1–S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). Results We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K–Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells. Conclusion In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future. Graphical Abstract

Long noncoding RNAs (lncRNAs) play essential roles in the development and progression of many cancers. However, the contributions of lncRNAs to medulloblastoma (MB) remain poorly understood. Here, we identify Miat as an lncRNA enriched in the sonic hedgehog group of MB that is required for maintenance of a treatment-resistant stem-like phenotype in the disease. Loss of Miat results in the differentiation of tumor-initiating, stem-like MB cells and enforces the differentiation of tumorigenic stem-like MB cells into a nontumorigenic state. Miat expression in stem-like MB cells also facilitates treatment resistance by down-regulating p53 signaling and impairing radiation-induced cell death, which can be reversed by therapeutic inhibition of Miat using antisense oligonucleotides. Mechanistically, the RNA binding protein Metadherin (Mtdh), previously linked to resistance to cytotoxic therapy in cancer, binds to Miat in stem-like MB cells. Like the loss of Miat, the loss of Mtdh reduces tumorigenicity and increases sensitivity to radiation-induced death in stem-like MB cells. Moreover, Miat and Mtdh function to regulate the biogenesis of several microRNAs and facilitate tumorigenesis and treatment resistance. Taken together, these data reveal an essential role for the lncRNA Miat in sustaining a treatment-resistant pool of tumorigenic stem-like MB cells.

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan‐neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle‐expression of LRG. At the molecular level, the synaptic vesicles (SVs) release and movement‐related SYT1 protein was recognized as LRG‐interacting protein candidate. Furthermore, LRG had no effects on SYT1 expression. Genetically, the behavioral defects in LRG mutant could be rescued by pan‐neuronal knock‐down of Syt1. Taken together, all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression. Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Persistent hyperglycemia has been identified as promoting neurovascular dysfunction, leading to irreversible endothelial dysfunction, increased neuronal apoptosis, oxidative stress and inflammation. These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy. Noncoding RNAs may provide a new strategy for understanding the etiology, pathogenesis and treatment of the disease. OBJECTIVE: To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad, in order to provide new ideas and approaches for noncoding RNAs in the prevention, diagnosis and treatment of diabetes neuropathy. METHODS: CNKI and PubMed were retrieved for relevant literature published from database inception to 2022. The key words were “noncoding RNA; lncRNA; miRNA; diabetes peripheral neuropathy; expression profile” in Chinese and English, respectively. The retrieved documents were summarized and analyzed, and 61 articles were finally selected for further review. RESULTS AND CONCLUSION: (1) Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy. Among the most widely studied regulatory noncoding RNA species, there are long noncoding RNAs, circular RNAs and microRNAs. (2) Through the regulation of noncoding RNAs, the activation or inhibition of related cell pathways, inflammatory genes and downstream-related cytokines will inhibit cell apoptosis, improve inflammation, and thus change the expression of target genes to participate in the process of diabetic neuralgia. (3) Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy, the mechanisms of many noncoding RNAs are unclear, and the same noncoding RNAs may play different roles in different modes. Therefore, it is necessary to further study their action modes in disease etiology and pathology, thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy. However, the criteria for evaluating noncoding RNA activity have not yet been established, and further research is needed on which specific noncoding RNAs play a dominant regulatory role. (4) MicroRNAs, long noncoding RNAs and their target genes can regulate progressive neuropathy, which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Chromatin instability plays a crucial role in multiple myeloma (MM) relapse and progression, but its mechanism remains obscure. Here, we uncovered that m6A-demethylase ALKBH5 upregulated and stabilized long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15), which was elevated in MM and positively correlated with unfavorable clinical prognosis factors. ALKBH5-SNHG15 axis participated in viability and migration/invasion of myeloma cell lines and MM-xenografted SCID/NOD mice. Mechanically, ALKBH5 promoted the expression of trimethylated histone H3 at lysine 36 (H3K36me3) methyltransferase SETD2 through lncRNA SNHG15-mediated protein stability. ALKBH5-SNHG15 axis increased chromatin accessibility and altered the H3K36me3 enrichment at the gene body, which is responsible for transcription elongation. Our study suggested a novel epigenetically interaction of N6-methyladenosine (m6A) methylation, lncRNA SNHG15, and histone SETD2/H3K36me3 modifications in myeloma progression, indicating that ALKBH5 and lncRNA SNHG15 could serve as potential novel therapeutic targets for MM treatment. [ABSTRACT FROM AUTHOR]

Although many long noncoding RNAs have been discovered in plants, little is known about their biological function and mode of action. Here we show that the drought-induced long intergenic noncoding RNA DANA1 interacts with the L1p/L10e family member protein DANA1-INTERACTING PROTEIN 1 (DIP1) in the cell nucleus of Arabidopsis, and both DANA1 and DIP1 promote plant drought resistance. DANA1 and DIP1 increase histone deacetylase HDA9 binding to the CYP707A1 and CYP707A2 loci. DIP1 further interacts with PWWP3, a member of the PEAT complex that associates with HDA9 and has histone deacetylase activity. Mutation of DANA1 enhances CYP707A1 and CYP707A2 acetylation and expression resulting in impaired drought tolerance, in agreement with dip1 and pwwp3 mutant phenotypes. Our results demonstrate that DANA1 is a positive regulator of drought response and that DANA1 works jointly with the novel chromatin-related factor DIP1 on epigenetic reprogramming of the plant transcriptome during the response to drought. Synopsis: During plant drought stress, the drought-induced lincRNA DANA1 works jointly with the DANA1 INTERACTING PROTEIN 1 (DIP1) to decrease the expression of CYP707A1 and CYP707A2 by facilitating HDA9-mediated histone deacetylation, thereby increasing ABA content and enhancing plant drought tolerance. DANA1 is a long intergenic noncoding RNA that promotes drought response in plants. DANA1 binds to the epigenetic regulator DIP1, and both DANA1 and DIP1 promote HDA9 binding to and deacetylation of the drought stress-responsive loci CYP707A1 and 2. During plant drought stress, the drought-induced lincRNA DANA1 works jointly with the DANA1 INTERACTING PROTEIN 1 (DIP1) to decrease the expression of CYP707A1 and CYP707A2 by facilitating HDA9-mediated histone deacetylation, thereby increasing ABA content and enhancing plant drought tolerance. [ABSTRACT FROM AUTHOR]

Introduction: Chronic lymphocytic leukemia (CLL) is characterized by a very heterogeneous clinical outcome. Thus, a plethora of prognostic factors and systems has been identified to place patients into different risk categories and to guide therapy decisions. The classic clinical staging models by Rai and Binet have been the cornerstone of patient management for several years. The greater insight into the molecular biology of CLL facilitated the advent of prognostic genetic biomarkers that are expected to impact clinical practice soon in the future. Therefore, we aimed to investigate the expression of long non‐coding RNA (lncRNA) CRNDE in patients with CLL, and to analyze its relationship with the clinicopathological parameters of CLL. Methods: In this study, 40 untreated CLL patients and 30 age‐ and gender‐matched controls were enrolled. The analysis of lncRNA CRNDE expression was determined using reverse transcription‐quantitative polymerase chain reaction technique. Results: Our result confirmed the downregulated expression of LncRNA CRNDE in CLL patients compared to controls (p < 0.001). The low expression of CRNDE was significantly associated with poor prognostic markers including advanced stage of CLL, high levels of serum beta‐2 microglobulin and lactic dehydrogenase, and the presence of del17p (p = 0.029, p = 0.013, p = 0.003, p = 0.028; respectively). Conclusion: Our study demonstrated that LncRNA CRNDE is significantly downregulated and associated with poor prognostic markers in CLL. It provides a rationale to assess its biological and prognostic impact in CLL. [ABSTRACT FROM AUTHOR]

LncRNAs have gained increasing attention owing to their important regulatory roles on growth and stress responses of plants. However, the mechanisms underlying the functions of lncRNAs in fruit‐pathogen interaction are still largely unknown. In this study, a total of 273 lncRNAs responding to Botrytis cinerea infection were identified in tomato fruit, among which a higher percentage of antisense lncRNAs were targeted to the genes enriched in hydrolase activity. To ascertain the roles of these lncRNAs, seven hydrolase‐related transcripts were transiently knocked‐down by virus‐induced gene silencing. Silencing of lncRNACXE20 reduced the expression level of a carboxylesterase gene, further enhancing the resistance of tomato to B. cinerea. In contrast, silencing of lncRNACHI, lncRNAMMP, lncRNASBT1.9 and lncRNAPME1.9 impaired the resistance to B. cinerea, respectively. Further RT‐qPCR assay and enzymatic activity detection displayed that the attenuated resistance of lncRNAMMP and lncRNASBT1.9‐silenced plants was associated with the inhibition on the expression of JA‐related genes, while the decreased resistance of lncRNACHI‐silenced plants resulted in reduced chitinase activity. Collectively, these results may provide references for deciphering the mechanisms underlying specific lncRNAs to interfere with B. cinerea infection by regulating the expression of defence‐related genes or affecting hydrolase activity. Summary Statement: To add more references to the mechanisms underlying the interaction between fruit—Botrytis cinerea interaction, the lncRNAs induced by B. cinerea in tomato fruit were identified and their roles were preliminarily investigated. The results revealed that specific lncRNAs are involved in fruit—B. cinerea interaction by regulating the expression of defence‐related genes or affecting hydrolase activity. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a prevalent type of gastrointestinal cancer, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. CYP1B1-AS1, as non-coding RNA, plays an important role in tumorigenesis and progression. However, the mechanism by which CYP1B1-AS1 acts in CRC is not yet understood. Aims: The objective of this study was to investigate how CYP1B1-AS1 contributes to the development of CRC, and provide a base for CRC diagnosis and treatment. Methods: RT-qPCR was used to detect the expression level of CYP1B1-AS1 in CRC and adjacent tissues. CCK-8, Edu, scratch healing, and transwell experiments were used to detect the changes of proliferation, migration, and invasion ability of CRC cells after overexpression or knockdown of CYP1B1-AS1 respectively. The RNA binding protein NOP58 combined with CYP1B1-AS1 was verified by RIP and RNA Pull-down experiments. Functional recovery experiments validated the interaction between CYP1B1-AS1 and NOP58 in CRC cells. The changes of EMT-related proteins were detected by Western blot, and the half-life of transcription factor SNAIL mRNA were detected by RT-qPCR after overexpression or knockdown of NOP58. Results: CYP1B1-AS1 was found to be significantly downregulated in CRC compared to adjacent noncancerous tissues. Experiments conducted in vitro and in vivo confirmed that upregulation of CYP1B1-AS1 significantly inhibited the proliferation, migration, and invasion of CRC cells. In addition, CYP1B1-AS1 can directly bind to NOP58 and negatively regulate NOP58. The effect of overexpression CYP1B1-AS1 was reversed by NOP58 overexpression. NOP58 regulates the EMT process of CRC cells by affecting the stability of EMT-related transcription factor SNAIL mRNA, and then affects the progress of CRC. Conclusion: This research proves that CYP1B1-AS1 can inhibit the occurrence of EMT in CRC by binding with NOP58, thus delaying the progress of CRC. This finding indicates that CYP1B1-AS1 may be a novel biomarker to improve the diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

Aims: Long noncoding RNAs (lncRNAs) may be associated with the development of type 2 diabetes mellitus and its complications; however, the findings remain controversial. We aimed to synthesize the available data to assess the diagnostic utility of lncRNAs for identification of type 2 diabetes mellitus and its consequences. Materials and Methods: We performed a systematic review and meta‐analysis, searching PubMed, Embase, and Web of Science for articles published from September 11, 2015 to December 27, 2022. We evaluated human case–control or cohort studies on differential lncRNA expression in type 2 diabetes mellitus or its associated comorbidities. We excluded studies if they were non‐peer reviewed or published in languages other than English. From 2387 identified studies, we included 17 (4685 participants). Results: Analysis of the pooled data showed that lncRNAs had a diagnostic area under the curve (AUC) of 0.84 (95% CI: 0.80–0.87), with a sensitivity of 0.79 (95% CI: 0.74–0.83) and a specificity of 0.75 (95% CI: 0.69–0.80). LncRNAs had an AUC of 0.65 for the diagnosis of prediabetes, with 82% sensitivity and 65% specificity. Conclusions: LncRNAs may be promising diagnostic markers for type 2 diabetes mellitus and its complications. [ABSTRACT FROM AUTHOR]

Chronic alcohol exposure results in widespread dysregulation of gene expression that contributes to the pathogenesis of Alcohol Use Disorder (AUD). Long noncoding RNAs are key regulators of the transcriptome that we hypothesize coordinate alcohol‐induced transcriptome dysregulation and contribute to AUD. Based on RNA‐Sequencing data of human prefrontal cortex, basolateral amygdala and nucleus accumbens of AUD versus non‐AUD brain, the human LINC01265 and its predicted murine homolog Gm41261 (i.e., TX2) were selected for functional interrogation. We tested the hypothesis that TX2 contributes to ethanol drinking and behavioral responses to ethanol. CRISPR/Cas9 mutagenesis was used to create a TX2 mutant mouse line in which 306 base‐pairs were deleted from the locus. RNA analysis revealed that an abnormal TX2 transcript was produced at an unchanged level in mutant animals. Behaviorally, mutant mice had reduced ethanol, gaboxadol and zolpidem‐induced loss of the righting response and reduced tolerance to ethanol in both sexes. In addition, a male‐specific reduction in two‐bottle choice every‐other‐day ethanol drinking was observed. Male TX2 mutants exhibited evidence of enhanced GABA release and altered GABAA receptor subunit composition in neurons of the nucleus accumbens shell. In C57BL6/J mice, TX2 within the cortex was cytoplasmic and largely present in Rbfox3+ neurons and IBA1+ microglia, but not in Olig2+ oligodendrocytes or in the majority of GFAP+ astrocytes. These data support the hypothesis that TX2 mutagenesis and dysregulation impacts ethanol drinking behavior and ethanol‐induced behavioral responses in mice, likely through alterations in the GABAergic system. [ABSTRACT FROM AUTHOR]

Recently, long noncoding RNAs (lncRNAs) have been applied as biomarkers for melanoma patients. In this systematic review and meta‐analysis, we investigated the diagnostic and prognostic value of lncRNAs. We used the keywords 'lncRNA' and 'melanoma' to search databases for studies published before June 14th, 2023. The specificity, sensitivity and AUC were utilized to assess diagnostic accuracy and the prognostic value was assessed using overall survival, progression‐free survival and disease‐free survival hazard ratios. After screening 1191 articles, we included seven studies in the diagnostic evaluation section and 17 studies in the prognosis evaluation section. The Reitsma bivariate model estimated a cumulative sensitivity of 0.724 (95% CI: 0.659–0.781, p < 0.001) and specificity of 0.812 (95% CI: 0.752–0.859, p < 0.001). The pooled AUC was 0.780 (95% CI: 0.749–0.811, p < 0.0001). The HR for overall survival was 2.723 (95% CI: 2.259–3.283, p < 0.0001). Two studies reported an HR for overall survival less than one, with an HR of 0.348 (95% CI: 0.200–0.607, p < 0.0002). The HR for progression‐free survival was 2.913 (95% CI: 2.050–4.138, p < 0.0001). Four studies reported an HR less than one, with an HR of 0.457 (95% CI: 0.256–0.817). The HR for disease‐free survival was 2.760 (95% CI: 2.009–3.792, p < 0.0001). In conclusion, the expression of lncRNAs in melanoma patients affects survival and prognosis. LncRNAs can also be employed as diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Chronic kidney disease（CKD） refers to chronic kidney structure and dys-function caused by various reasons, and renal fibrosis is one of its common pathological ma-nifestations, mainly including the entire process of renal function from damage to complete loss. Long noncoding RNA（lncRNA）,as a type of non protein coding RNA,has a wide variety of types and is widely involved in various cellular biological regulatory processes in the body. It can regulate microRNAs activity, control the expression of target genes, and participate in the occurrence and evolution of various diseases, including CKD. The occurrence of chronic kidney diseases such as diabetes nephropathy, obstructive nephropathy and lupus nephritis is related to renal fibrosis, and is closely related to a variety of lncRNA and corresponding molecular signal pathways. This provides some safer and more reliable new treatment approaches for the prevention and treatment of CKD. [ABSTRACT FROM AUTHOR]

Abiotic/biotic stresses pose a major threat to agriculture and food security by impacting plant growth, productivity and quality. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long non-coding RNAs (lncRNAs) with sizes larger than 200 nucleotides in length, provides an important new perspective on the centrality of RNA in gene regulation. In plants, lncRNAs are widespread and fulfill multiple biological functions in stress response. In this paper, the research advances on the biological function of lncRNA in plant stress response were summarized, like as Natural Antisense Transcripts (NATs), Competing Endogenous RNAs (ceRNAs) and Chromatin Modification etc. And in plants, lncRNAs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid (ABA), jasmonate (JA), salicylic acid (SA) and redox signaling in response to many abiotic/biotic stresses. Moreover, conserved sequence motifs and structural motifs enriched within stress-responsive lncRNAs may also be responsible for the stress-responsive functions of lncRNAs, it will provide a new focus and strategy for lncRNA research. Taken together, we highlight the unique role of lncRNAs in integrating plant response to adverse environmental conditions with different aspects of plant growth and development. We envisage that an improved understanding of the mechanisms by which lncRNAs regulate plant stress response may further promote the development of unconventional approaches for breeding stress-resistant crops. [ABSTRACT FROM AUTHOR]

Circadian rhythm disorders pose major risks to human health and animal production activity, and the hypothalamus is the center of circadian rhythm regulation. However, the epigenetic regulation of circadian rhythm based on farm animal models has been poorly investigated. We collected chicken hypothalamus samples at seven time points in one light/dark cycle and performed long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA sequencing to detect biomarkers associated with circadian rhythm. We enhanced the comprehensive expression profiling of ncRNAs and mRNAs in the hypothalamus and found two gene sets (circadian rhythm and retinal metabolism) associated with the light/dark cycle. Noncoding RNA networks with circadian expression patterns were identified by differential expression and circadian analysis was provided that included 38 lncRNAs, 15 circRNAs, and 200 candidate genes. Three lncRNAs (ENSGALT00000098661, ENSGALT00000100816, and MSTRG.16980.1) and one circRNA (novel_circ_010168) in the ncRNA–mRNA regulatory network were identified as key molecules influencing circadian rhythm by regulating AOX1 in retinal metabolism. These ncRNAs were predicted to be related to pernicious anemia, gonadal, eye disease and other disorders in humans. Together, the findings of this study provide insights into the epigenetic mechanisms of circadian rhythm and reveal AOX1 as a promising target of circadian rhythm regulation. [ABSTRACT FROM AUTHOR]

Background: Inflammation is the major contributor to the pathophysiology of ischemic stroke (IS). Long non-coding ribonucleic acids (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory (THRIL) have been demonstrated to be up-regulated in inflammation and atherosclerosis. Therefore, we aimed to study the expression profile of these lncRNAs after IS. Methods: This observational case-control study was conducted in Namazi Hospital, Shiraz, Iran. The real-time polymerase chain reaction (RT-PCR) measured the sequential changes in circulating levels of MALAT1 and THRIL on days 1, 3, and 5 after IS. The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic and prognostic potential of lncRNAs with the area under the curve (AUC). Results: In patients with IS, the relative MALAT1 and THRIL expressions were significantly higher than the controls (P < 0.001 and P < 0.01, respectively), on days 1, 3, and 5 after stroke. [ABSTRACT FROM AUTHOR]

Oxygen is an essential factor for the body's metabolism and survival. Hypoxic adaptation refers to a series of local and systemic changes that occur in the body to adapt to the physiological or pathological phenomenon of hypoxia, reducing the impact of hypoxia. Competing endogenous RNA (ceRNA) refers to RNA molecules that share the same microRNA response elements (MREs) and competitively bind to microRNAs to regulate gene expression at the post- transcriptional level, thereby influencing the biological functions of cells. ceRNA is a complex network regulation mechanism that plays a role in cell proliferation and apoptosis, inflammatory responses, energy metabolism, muscle development, fat deposition, lipid metabolism, and other aspects. The article summarizes the biological functions and characteristics of long noncoding RNA (lncRNA), circular RNA (circRNA), and pseudogenes. It elucidates the validated roles of ceRNA in the biological functions associated with animal hypoxic adaptation, providing reference for the study of mammalian hypoxia adaptability. [ABSTRACT FROM AUTHOR]

In recent years, accumulating evidence has demonstrated the role of long noncoding RNAs (lncRNAs) in colon cancer. We aim to investigate the role of MIR143HG, also known as CARMN (Cardiac mesoderm enhancer‐associated noncoding RNA) in colon cancer and explore the related mechanisms. An RNAseq data analysis was performed to screen differentially expressed lncRNAs associated with colon cancer. Next, MIR143HG expression was quantified in colon cancer cells. Moreover, the contributory roles of MIR143HG in the progression of colon cancer with the involvement of DNMT1 and HOXB7 (Homeobox B7) were evaluated after restored MIR143HG or depleted HOXB7. Finally, the effects of MIR143HG were investigated in vivo by measuring tumor formation in nude mice. High‐throughput transcriptome sequencing was employed to validate the specific mechanisms by which MIR143HG and HOXB7 affect tumor growth in vivo. MIR143HG was found to be poorly expressed, while HOXB7 was highly expressed in colon cancer. MIR143HG could promote HOXB7 methylation by recruiting DNMT1 to reduce HOXB7 expression. Upregulation of MIR143HG or downregulation of HOXB7 inhibited cell proliferation, invasion and migration and facilitated apoptosis in colon cancer cells so as to delay the progression of colon cancer. The same trend was identified in vivo. Our study provides evidence that restoration of MIR143HG suppressed the progression of colon cancer via downregulation of HOXB7 through DNMT1‐mediated HOXB7 promoter methylation. Thus, MIR143HG may be a potential candidate for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Summary: Aluminium (Al) toxicity decreases crop production in acid soils in general, but many crops have evolved complex mechanisms to resist it. However, our current understanding of how plants cope with Al stress and perform Al resistance is still at the initial stage. In this study, the citrate transporter CcMATE35 was identified to be involved in Al stress response. The release of citrate was increased substantially in CcMATE35 over‐expression (OE) lines under Al stress, indicating enhanced Al resistance. It was demonstrated that transcription factor CcNFYB3 regulated the expression of CcMATE35, promoting the release of citrate from roots to increase Al resistance in pigeon pea. We also found that a Long noncoding RNA Targeting Citrate Synthase (CcLTCS) is involved in Al resistance in pigeon pea. Compared with controls, overexpression of CcLTCS elevated the expression level of the Citrate Synthase gene (CcCS), leading to increases in root citrate level and citrate release, which forms another module to regulate Al resistance in pigeon pea. Simultaneous overexpression of CcNFYB3 and CcLTCS further increased Al resistance. Taken together, these findings suggest that the two modules, CcNFYB3‐CcMATE35 and CcLTCS‐CcCS, jointly regulate the efflux and synthesis of citrate and may play an important role in enhancing the resistance of pigeon pea under Al stress. [ABSTRACT FROM AUTHOR]

Summary: Long noncoding RNAs (lncRNAs) play an important role in abiotic stress tolerance. However, their function in conferring abiotic stress tolerance is still unclear. Herein, we characterized the function of a salt‐responsive nuclear lncRNA (BplncSIR1) from Betula platyphylla (birch). Birch plants overexpressing and knocking out for BplncSIR1 were generated. BplncSIR1 was found to improve salt tolerance by inducing antioxidant activity and stomatal closure, and also accelerate plant growth. Chromatin isolation by RNA purification (ChIRP) combined with RNA sequencing indicated that BplncSIR1 binds to the promoter of BpNAC2 (encoding NAC domain‐containing protein 2) to activate its expression. Plants overexpressing and knocking out for BpNAC2 were generated. Consistent with that of BplncSIR1, overexpression of BpNAC2 also accelerated plant growth and conferred salt tolerance. In addition, BpNAC2 binds to different cis‐acting elements, such as G‐box and 'CCAAT' sequences, to regulate the genes involved in salt tolerance, resulting in reduced ROS accumulation and decreased water loss rate by stomatal closure. Taken together, BplncSIR1 serves as the regulator of BpNAC2 to induce its expression in response to salt stress, and activated BpNAC2 accelerates plant growth and improves salt tolerance. Therefore, BplncSIR1 might be a candidate gene for molecular breeding to cultivate plants with both a high growth rate and improved salt tolerance. [ABSTRACT FROM AUTHOR]

There is no doubt that the incidence of cancer sufferers is rising in the world, and it is estimated that in the next several decades, the number of people suffering from malignancies or the cancer rate will double. Diagnostic and therapeutic targeting of noncoding RNAs (ncRNAs), especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), represent an excellent approach for cancer diagnosis and treatment, as well as many other diseases. One of the latest miRNAs is miR-4492, upregulating some genes in tumor tissues including ROMO1, HLA-G, NKIRAS2, FOXK1, and UBE2C. It represents an attractant example of a miRNA acting at multiple levels to affect the same malignancy hallmark. Based on the studies, miR-4492 plays a key role in several cancers such as, breast cancer, bladder cancer, osteosarcoma, glioblastoma multiforme, hepatocellular carcinoma, colorectal cancer, and ovarian cancer. Putting it all together, identifying the precise mechanisms of miR-4492 in the pathogenesis of cancer, could pave the way to find better diagnostic and therapeutic strategies for cancer sufferers. For this reason, it might be a novel potential diagnostic biomarker and therapeutic target for neoplasms. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) presents a significant global health threat, particularly in regions endemic to hepatitis B and C viruses, and because of the ongoing pandemic of obesity causing metabolic-dysfunction-related fatty liver disease (MAFLD), a precursor to HCC. The molecular intricacies of HCC, genetic and epigenetic alterations, and dysregulated signaling pathways facilitate personalized treatment strategies based on molecular profiling. Epigenetic regulation, encompassing DNA methyltion, histone modifications, and noncoding RNAs, functions as a critical layer influencing HCC development. Long noncoding RNAs (lncRNAs) are spotlighted for their diverse roles in gene regulation and their potential as diagnostic and therapeutic tools in cancer. In this review, we explore the pivotal role of lncRNAs in HCC, including MAFLD and viral hepatitis, the most prevalent risk factors for hepatocarcinogenesis. The dysregulation of lncRNAs is implicated in HCC progression by modulating chromatin regulation and transcription, sponging miRNAs, and influencing structural functions. The ongoing studies on lncRNAs contribute to a deeper comprehension of HCC pathogenesis and offer promising routes for precision medicine, highlighting the utility of lncRNAs as early biomarkers, prognostic indicators, and therapeutic targets. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), the most aggressive primary malignant brain tumor, is resistant to conventional radiotherapies and chemotherapies, including temozolomide (TMZ). Overcoming GBM resistance to the chemotherapeutic agent TMZ poses an important therapeutic problem. This study established an association between the long noncoding RNA TP73-AS1 and TMZ sensitivity regulation in human GBM cells (U87MG). Transcriptomic analysis revealed that TP73-AS1 expression was reduced in TMZ-resistant U87MGRT100 cells compared to that in parental U87MG cells. Additionally, TP73-AS1 knockdown in parental U87MG cells decreased their sensitivity to TMZ. Overall, these findings suggest that TP73-AS1 functions as a regulator of TMZ sensitivity in GBM cells. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are associated with many dermatologic diseases. However, little is known about the regulatory function of lncRNAs in familial acne inversa (AI) patients with nicastrin (NCSTN) mutation. Objectives: The aim of this study was to explore the regulatory function of lncRNAs in familial AI patients with NCSTN mutation. Methods: The expression profiles of lncRNAs and mRNAs in skin tissues from familial AI patients with NCSTN mutation and healthy individuals were analysed in this study via RNA sequencing (RNA-seq). Results: In total, 359 lncRNAs and 1,863 mRNAs were differentially expressed between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the dysregulated mRNAs targeted by lncRNAs were mainly associated with the immune regulation, Staphylococcus aureus infection and B cell receptor signalling pathways. The lncRNA-miRNA-mRNA coexpression network contained 265 network pairs comprising 55 dysregulated lncRNAs, 11 miRNAs, and 74 mRNAs. Conservation analysis of the differentially expressed lncRNAs between familial AI patients with NCSTN mutation and Ncstn keratinocyte-specific knockout (NcstnΔKC) mice identified 6 lncRNAs with sequence conservation; these lncRNAs may participate in apoptosis, proliferation, and skin barrier function. Conclusions: These findings provide a direction for exploring the regulatory mechanisms underlying the progression of familial AI patients with NCSTN mutation. [ABSTRACT FROM AUTHOR]

Breast cancer is the most lethal form of cancer in women, and patients face serious health risks. Long non-coding RNAs are involved in a variety of regulatory processes and can influence cancers development at different levels. This study aimed to introduce a central regulatory lncRNA based on differentially expressed proteins in breast cancer and evaluate its expression level in breast tissues. In this study, proteomic data was obtained from ProteomeXchange and then differentially expressed proteins were detected. The Enrichr database was used to identify the regulatory factors of differentially expressed proteins, and functional enrichment analysis was used to demonstrate key signaling pathways and biological processes. Eventually, a lncRNA with the highest rank in the central hub was chosen, and its expression level was measured by RT-qPCR in 15 breast cancer tissues and their adjacent nontumor tissues. Proteomic analysis recognized 1149 differential expressed proteins in breast cancer with regulatory agents consisting of 76 TFs, 61 kinases, 366 miRNAs, and 162 lncRNAs. A multi-regulatory network with 1811 nodes and 4022 edges was constructed based on differentially expressed proteins and their associated elements. In addition, these regulatory elements were related to three biological functions and 11 pathways. Finally, bioinformatic analysis identified lncRNA WWTR1-AS1 as having the highest node score involved in different mechanisms. Functional experiments confirmed that the expression level of the lncRNA WWTR1-AS1 was significantly increased in breast cancer patients. ROC analysis suggested that this lncRNA can be used as a reliable biomarker. Our data provide evidence that the lncRNA WWTR1-AS1 is an effective factor in the regulation of DEPs, is associated with malignant features in breast cancer, and might be useful as a prognostic marker in Breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non‐coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR‐877‐3p/GZMB axis. Subsequently, exosomes (CT‐Exo‐siISSRL‐oeGH) with precise cartilage‐targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non‐coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Abstract Background Acute myeloid leukemia (AML) is aggressive type of hematological malignancy. Its poses challenges in early diagnosis, necessitating the identification of an effective biomarker. This study aims to assess the diagnostic accuracy of long noncoding RNAs (lncRNA) in the diagnosis of AML through a meta‐analysis. The study is registered on the PROSPERO website with the number 493518. Method A literature search was conducted in the PubMed, Embase, Hinari, and the Scopus databases to identify relevant studies. We pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristics (ROC) using Stata 14.1 software. Heterogeneity between studies was determined through the I2 statistic and Cochran‐Q test. A random effect model was chosen due to significant heterogeneity among included studies. Meta‐regression and subgroup analysis were performed to assess the potential source of heterogeneity. Furthermore, potential publication bias was estimated using Deek's funnel plot asymmetry test. Results A total of 14 articles covering 19 studies were included in this meta‐analysis comprising 1588 AML patients and 529 healthy participants. The overall pooled sensitivity, specificity, PLR, NLR, DOR, and the area under the summary ROC curve were 0.85 (95% CI = 0.78–0.91), 0.82 (95% CI = 0.72–0.89), 4.7 (95% CI = 2.9–7.4), 0.18 (95% CI = 0.12–0.28), 26 (95% CI = 12–53), and 0.90 (95% CI = 0.87–0.93), respectively. Moreover, lncRNAs from non‐bone marrow mononuclear cells (BMMC) had superior diagnostic value with pooled sensitivity, specificity, and AUC were 0.93, 0.82, and 0.95, respectively. Conclusion This meta‐analysis demonstrated that circulating lncRNAs can serve as potential diagnostic markers for AML. High accuracy of diagnosis was observed in non‐BMMC lncRNAs, given cutoff value, and the GADPH internal reference gene used. However, further studies with large sample size are required to confirm our results.

Background Long noncoding RNAs (lncRNAs) have emerged as critical regulators of the expression of genes involved in cardiovascular diseases. This project aims to identify circulating lncRNAs associated with protein‐coding mRNAs differentially expressed between hypertensive and normotensive individuals and establish their link with hypertension. Methods and Results The analyses were conducted in 3 main steps: (1) an unbiased whole blood transcriptome‐wide analysis was conducted to identify and replicate protein‐coding genes differentially expressed by hypertension status in 497 and 179 Black individuals from the GENE‐FORECAST (Genomics, Environmental Factors and the Social Determinants of Cardiovascular Disease in African‐Americans Study) and MH‐GRID (Minority Health Genomics and Translational Research Bio‐Repository Database) studies, respectively. Subsequently, (2) proximal lncRNAs, termed cis lncRNA quantitative trait loci, associated with each mRNA were identified in the GENE‐FORECAST study and replicated in the MH‐GRID study. Finally, (3) the lncRNA quantitative trait loci were used as predictors in a random forest model to predict hypertension in both data sets. A total of 129 mRNAs were significantly differentially expressed between normotensive and hypertensive individuals in both data sets. The lncRNA‐mRNA association analysis revealed 249 cis lncRNA quantitative trait loci associated with 102 mRNAs, including VAMP2 (vesicle‐associated membrane protein 2), mitogen‐activated protein kinase kinase 3, CCAAT enhancer binding protein beta, and lymphocyte antigen 6 complex, locus E. The 249 lncRNA quantitative trait loci predicted hypertension with an area under the curve of 0.79 and 0.71 in GENE‐FORECAST and MH‐GRID studies, respectively. Conclusions This study leveraged a significant sample of Black individuals, a population facing a disproportionate burden of hypertension. The analyses unveiled a total of 271 lncRNA‐mRNA relationships involving mRNAs that play critical roles in vascular pathways relevant to blood pressure regulation. The compelling findings, consistent across 2 independent data sets, establish a reliable foundation for designing in vitro/in vivo experiments.

Abstract Background Esophageal cancer (ESCA) is a highly invasive malignant tumor with poor prognosis. This study aimed to discover a generalized and high‐sensitivity immune prognostic signature that could stratify ESCA patients and predict their overall survival, and to discover potential therapeutic drugs by the connectivity map. Methods The key gene modules significantly related to clinical traits (survival time and state) of ESCA patients were selected by weighted gene coexpression network analysis (WCGNA), then the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a 15‐immune‐related gene prognostic signature. Results The immune‐related risk model was related to clinical and pathologic factors and remained an effective independent prognostic factor. Enrichment analyses revealed that the differentially expressed genes (DEGs) of the high‐ and low‐risk groups were associated with tumor cell proliferation and immune mechanisms. Based on the gathered data, a small molecule drug named perphenazine (PPZ) was elected. The pharmacological analysis indicates that PPZ could help in adjuvant therapy of ESCA through regulation of metabolic process and cellular proliferation, enhancement of immunologic functions, and inhibition of inflammatory reactions. Furthermore, molecular docking was performed to explore and verify the PPZ‐core target interactions. Conclusion We succeed in structuring the immune‐related prognostic model, which could be used to distinguish and predict patients' survival outcome, and screening a small molecule drug named PPZ. Prospective studies also are needed to further validate its analytical accuracy for estimating prognoses and confirm the potential use of PPZ for treating ESCA.