Mechanisms Of lncRNAs Research Articles

Long noncoding RNAs and their complex role in shaping and regulating arachidonic acid metabolism: Learning to love the (not-really) junk.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators in numerous biological processes. The arachidonic acid (AA) metabolic pathway is a fundamental biochemical pathway responsible for the enzymatic conversion of AA, a 20-carbon omega-six polyunsaturated fatty acid, into a variety of potent lipid signaling molecules known as eicosanoids. Eicosanoids are produced through the cyclooxygenase and lipoxygenase arms of the AA pathway and have diverse biological roles in both healthy and disease states, including cancer and inflammatory diseases. Cyclooxygenase 2 (COX-2), the inducible, rate-limiting enzyme of the cyclooxygenase arm, produces two main forms of eicosanoids: prostaglandins and thromboxanes. AA metabolized through the lipoxygenase arm by the action of 5-lipoxygenase (ALOX5) produces eicosanoids known as leukotrienes. COX-2 and ALOX5 gene expression are regulated through many different lncRNAs and microRNA (miRNA)-mediated mechanisms. As previously reviewed, noncoding RNAs affect transcription, splicing, alternative polyadenylation, messenger RNA stability, translation, and miRNA regulation of COX-2 and ALOX5 (Lutz and Cornett, 2013, Wiley Interdisciplinary Reviews. RNA, 4(5), 593-605). This current review discusses the intricate roles of lncRNAs, including MALAT1, NEAT1, HOTAIR, PACER, and others, in modulating the AA pathway. In this review update, we will delve into advancements in our understanding of AA gene expression regulation. We will explore the mechanisms of lncRNAs and their associated miRNAs and proteins known to regulate key components of the AA signaling pathway. We will also discuss the therapeutic potential of targeting lncRNA-mediated regulation, with a focus on modulating COX-2 and ALOX5 activity and downstream eicosanoid production for applications in inflammatory and oncological conditions. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease.

LncSEA 2.0: an updated platform for long non-coding RNA related sets and enrichment analysis.

Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs.

Long Non-Coding RNA as a Potential Biomarker for Canine Tumors.

Cancer is the leading cause of death in both humans and companion animals. Long non-coding RNA (lncRNA) plays a crucial role in the progression of various types of cancers in humans, involving tumor proliferation, metastasis, angiogenesis, and signaling pathways, and acts as a potential biomarker for diagnosis and targeted treatment. However, research on lncRNAs related to canine tumors is in an early stage. Dogs have long been considered a promising natural model for human disease. This article summarizes the molecular function of lncRNAs as novel biomarkers in various types of canine tumors, providing new insights into canine tumor diagnosis and treatment. Further research on the function and mechanism of lncRNAs is needed, which will benefit both human and veterinary medicine.

Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterusalbus

BackgroundMonopterusalbus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.MethodsWe produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.ResultsThis effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.ConclusionsThis study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M.albus, which will also enrich the sex differentiation mechanism of teleosts.

Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339

BackgroundFunctioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus.ResultsWe identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis.ConclusionsOur findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.

A TGF-β signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

The dysregulation of TGF-β signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-β signaling in glioma is currently unclear. Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. Invitro and invivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. In glioma, a TGF-β signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in invitro and invivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-β signaling pathway. A prognostic lncRNA signature of TGF-β signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

PTBP2 binds to a testis-specific long noncoding RNA, Tesra, and activates transcription of the Prss42/Tessp-2 gene

Long noncoding RNAs (lncRNAs) have recently been proved to be functional in the testis. Tesra, a testis-specific lncRNA, was suggested to activate the transcription of Prss42/Tessp-2, a gene that is involved in meiotic progression, in mouse spermatocytes. To reveal the molecular mechanism underlying the activation, we searched for Tesra-binding proteins by a Ribotrap assay followed by LC-MS/MS analysis and identified polypyrimidine tract binding protein 2 (PTBP2) as a candidate. Analysis of public RNA-seq data and our qRT-PCR results indicated that Ptbp2 mRNA showed an expression pattern similar to the expression patterns of Tesra and Prss42/Tessp-2 during testis development. Moreover, PTBP2 was found to be associated with Tesra in testicular germ cells by RNA immunoprecipitation. To evaluate the effect of PTBP2 on the Prss42/Tessp-2 promoter, we established an in vitro reporter gene assay system in which Tesra expression could be induced by the Tet-on system and thereby Prss42/Tessp-2 promoter activity could be increased. In this system, the Prss42/Tessp-2 promoter activity was significantly decreased by the knockdown of PTBP2. These results suggest that PTBP2 contributes to Prss42/Tessp-2 transcriptional activation by Tesra in spermatocytes. The finding provides a precious example of a molecular mechanism of testis lncRNA functioning in spermatogenesis.

Full-Length Transcriptome and the Identification of lncRNAs Involved in Salicylic Acid-Induced Flowering in Duckweed (Lemna gibba)

Long noncoding RNAs (lncRNAs) are crucial components in regulating the flowering of plants. However, the regulatory mechanism of lncRNAs underlying salicylic acid (SA)-induced flowering remains unknown in duckweed (e.g., Lemna gibba L.), an aquatic model species with significant potential applications in agriculture and industry. In this work, L. gibba plants were collected at four crucial time points during SA-induced flowering and subjected to PacBio full-length sequencing and strand-specific RNA sequencing. A total of 474 lncRNAs were identified, of which 31 were differentially expressed and involved in SA-induced flowering. A trans-regulatory analysis found that these lncRNAs displayed temporal-specific expression trends and mainly participated in stress metabolism, photosynthesis, jasmonate metabolism, and transport under SA treatment. Five lncRNAs were determined to act as targets of miRNAs that played critical roles in regulating flowering. In addition, fifteen lncRNAs showed co-expression with flowering-related genes, and lncRNA03 and lncRNA25 were identified as key players involved in flowering via lncRNA-miRNA-mRNA interactions. Finally, twelve lncRNAs related to trans-regulation, miRNA targets, or co-expression with flowering-related genes were verified by qRT-PCR. These findings deepen our understanding of lncRNAs in SA-induced flowering in duckweed and provide valuable resources for in-depth functional analysis in the future.

The mechanical and functional research of lncRNA, miRNA and genes

Societal progress parallels disease evolution, demanding swift exploration of disease mechanisms and innovative therapies, with recent emphasis on microRNA (miRNA) and long non-coding RNA (lncRNA) in intron regions. It is worthy of noticing to integrate the function and mechanism of lncRNA, microRNA and related genes, so as to provide integrate information for researchers in a clearer train of thought. Here, using the literature summarizing method, the keywords "lncRNA”, “mRNA” and “genes” were entered in PUBMED (https://pubmed.ncbi.nlm.nih.gov/) to obtain recent literature. Subsequently, we compressed, categorized and summarized these literature and reported. As a result, we systematically summarized the Research progress in the mechanism and function of the gene and lncRNA, the function and mutual mechanism of microRNA and gene, and relation of lncRNA and microRNA, so as to provide important literature information for understanding the mechanical and functional research of lncRNA, miRNA and genes.

Long noncoding RNA TRABA suppresses β-glucosidase-encoding BGLU24 to promote salt tolerance in cotton.

Salt stress severely damages the growth and yield of crops. Recently, long noncoding RNAs (lncRNAs) were demonstrated to regulate various biological processes and responses to environmental stresses. However, the regulatory mechanisms of lncRNAs in cotton (Gossypium hirsutum) response to salt stress are still poorly understood. Here, we observed that a lncRNA, trans acting of BGLU24 by lncRNA (TRABA), was highly expressed while GhBGLU24-A was weakly expressed in a salt-tolerant cotton accession (DM37) compared to a salt-sensitive accession (TM-1). Using TRABA as an effector and proGhBGLU24-A-driven GUS as a reporter, we showed that TRABA suppressed GhBGLU24-A promoter activity in double transgenic Arabidopsis (Arabidopsis thaliana), which explained why GhBGLU24-A was weakly expressed in the salt-tolerant accession compared to the salt-sensitive accession. GhBGLU24-A encodes an endoplasmic reticulum (ER)-localized β-glucosidase that responds to salt stress. Further investigation revealed that GhBGLU24-A interacted with RING-type E3 ubiquitin ligase (GhRUBL). Virus-induced gene silencing (VIGS) and transgenic Arabidopsis studies revealed that both GhBGLU24-A and GhRUBL diminish plant tolerance to salt stress and ER stress. Based on its substantial effect on ER-related degradation (ERAD)-associated gene expression, GhBGLU24-A mediates ER stress likely through the ERAD pathway. These findings provide insights into the regulatory role of the lncRNA TRABA in modulating salt and ER stresses in cotton and have potential implications for developing more resilient crops.

LncRNA SPRY4-IT1 regulates 16HBE cell malignant transformation induced by particulate matter through DUSP6-ERK1/2-Chk1 signaling pathway

Particulate matter (PM), one of the most serious air contaminants, could easily pass through the airway and deposit at the deep alveoli. Thus, it might trigger respiratory diseases like inflammation, asthma and lung cancer on human. Long non-coding RNAs (lncRNAs) are considered as important regulator in promotion and progression of diverse cancers. However, the molecular mechanism of lncRNAs mediating PM-induced lung carcinogenesis remains unclear. In this study, we established a 16HBE malignant transformed cell induced by PM (Cells were treated with 20 μg/ml PM, which named PM-T cells) and explored the roles and mechanisms of lncRNAs in the malignant transformation induced by PM. Compared with 16HBE cells, various biological functions were changed in PM-T cells, such as cell proliferation, migration, cell cycle and apoptosis. LncRNA SPRY4-IT1 was significant down-regulated expression and associated with these biological effects. Our results showed that lncRNA SPRY4-IT1 overexpression reversed these functional changes mentioned above. The further studies indicated that lncRNA SPRY4-IT1 involved in PM-induced cell transformation by modulating Chk1 expression via negative regulation of DUSP6-ERK1/2. In conclusion, our studies suggested that lncRNA SPRY4-IT1 played the role as a tumor suppressor gene and might mediate 16HBE cells malignant transformation induced by PM through regulating DUSP6-ERK1/2-Chk1 signaling pathway.

Predicting Plant miRNA-lncRNA Interactions via a Deep Learning Method.

In recent years, due to the contribution to elucidating the functional mechanisms of miRNAs and lncRNAs, the research on miRNA-lncRNA interaction prediction has increased exponentially. However, the prediction research is challenging in bioinformatics domain. It is expensive and time-consuming to verify the interactions by biological experiments. The existing prediction models have some limitations, such as the need to manually extract features, the potential loss of features from pre-treatment approaches, long-distance dependency to be solved, and so on. Additionally, most of the current models prefer to the animal data. However, the establishment of an efficient and accurate plant miRNA-lncRNA interaction prediction model is necessary. In this work, a new deep learning model called PmlIPM is presented to infer plant miRNA-lncRNA associations. PmlIPM is a four-step framework including Input Embedding, Positional Encoding, Multi-Head Attention and Max Pooling. PmlIPM accepts separately input of miRNA and lncRNA to extract sequence features, avoiding information loss caused by direct splicing the two sequences as model inputs. The attention mechanisms give the model the ability to capture long distance features. PmlIPM is compared with the existing models on 2 benchmark datasets. The results show that our model performs better than other methods and obtains AUC scores of 0.8412, 0.8587, 0.9666 and 0.9225 in the four independent test sets of Arabidopsis lyrata (A.ly), Solanum lycopersicum (S.ly), Brachypodium distachyon (B.di) and Solanum tuberosum (S.tu), respectively.

The Role of lncRNAs in Pig Muscle in Response to Cold Exposure.

Cold exposure is an essential factor affecting breeding efforts in cold regions. Muscle, as an important tissue for homeothermic animals, can produce heat through shivering thermogenesis (ST) and non-shivering thermogenesis (NST) under cold exposure. Long non-coding RNAs (lncRNAs) play important roles in regulating gene expression. However, the regulatory mechanisms of lncRNAs and their role in the thermogenesis of pigs are unclear. We examined lncRNAs in the skeletal muscle of an indigenous pig breed, the Enshi black pig, when the pigs were exposed to acute or chronic cold. Three pigs were maintained inside a pig house (control group), three pigs were maintained outside the pig house for 55 d (chronic cold group), and three pigs were suddenly exposed to the conditions outside the pig house for 3 days (acute cold group). After the experiment, the longissimus dorsi of each pig were collected, and their lncRNA profiles were sequenced and analyzed. Each sample obtained nearly 12.56 Gb of clean data. A total of 11,605 non-coding RNAs were obtained, including 10,802 novel lncRNAs. The number of differentially expressed lncRNAs (DElncRNAs) was identified under acute cold (427) and cold acclimation (376), with 215 and 192 upregulated lncRNAs, respectively. However, only 113 lncRNAs were commonly upregulated by acute cold and cold acclimation. In addition, 65% of the target genes were trans-regulated by DElncRNAs. The target genes were enriched in signal transduction, immune system, cell growth and death pathways, and amino acid and carbohydrate metabolism. Compared to cold acclimation, acute cold stress-induced more DElncRNAs and response pathways. In conclusion, low temperatures altered the expression levels of lncRNAs and their target genes in muscle tissue. Some potential mechanisms were revealed, including ion migration and the metabolism of amino acids and carbohydrates.

Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD

BackgroundTriple-negative breast cancer (TNBC) is a subtype of breast cancer with higher aggressiveness and poorer outcomes. Recently, long non-coding RNAs (lncRNAs) have become the crucial gene regulators in the progression of human cancers. However, the function and underlying mechanisms of lncRNAs in TNBC remains unclear.MethodsBased on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD.ResultsLncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD.ConclusionsCollectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.

Basement Membrane-Associated lncRNA Risk Model Predicts Prognosis and Guides Clinical Treatment in Clear Cell Renal Cell Carcinoma.

The basement membrane (BM) affects the invasion and growth of malignant tumors. The role and mechanism of BM-associated lncRNAs in clear cell renal cell carcinoma (ccRCC) are unknown. In this study, we identified biomarkers of ccRCC and developed a risk model to assess patient prognosis. We downloaded transcripts and clinical data from the Cancer Genome Atlas (TCGA). Differential analysis, co-expression analysis, Cox regression analysis, and lasso regression were used to identify BM-associated prognostic lncRNAs and create a risk prediction model. We evaluated and validated the accuracy of the model using multiple methods and constructed a nomogram to predict the prognosis of ccRCC. GO, KEGG, and immunity analyses were used to explore differences in biological function. We constructed a risk model containing six BM-associated lncRNAs (LINC02154, IGFL2-AS1, NFE4, AC112715.1, AC092535.5, and AC105105.3). The risk model has higher diagnostic efficiency compared to clinical characteristics and can be used to forecast patient prognoses. We used renal cancer cells and tissue microarrays to verify the expression of lncRNAs in the risk model. We found that knocking down LINC02154 and AC112715.1 could inhibit the invasion ability of renal cancer cells. The risk model based on BM-associated lncRNAs can well predict ccRCC and guide clinical treatment.

Long non-coding RNAs with essential roles in neurodegenerative disorders.

Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number of long non-coding RNAs (lncRNAs) have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns, across different neurodegenerative diseases. However, the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood. This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles, regulatory mechanisms, and research status of lncRNAs in Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Finally, this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases, hoping to provide broader implications for developing effective treatments.

Insights into the involvement of long non-coding RNAs in doxorubicin resistance of cancer.

Doxorubicin is one of the most classical chemotherapeutic drugs for the treatment of cancer. However, resistance to the cytotoxic effects of doxorubicin in tumor cells remains a major obstacle. Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with tumorigenesis and development via regulation of chromatin remodeling, transcription, and post-transcriptional processing. Emerging studies have also revealed that dysregulation of lncRNAs mediates the development of drug resistance through multiple molecules and pathways. In this review, we focus on the role and mechanism of lncRNAs in the progress of doxorubicin resistance in various cancers, which mainly include cellular drug transport, cell cycle disorder, anti-apoptosis, epithelial-mesenchymal transition, cancer stem cells, autophagy, tumor microenvironment, metabolic reprogramming and signaling pathways. This review is aimed to provide potential therapeutic targets for future cancer therapy, especially for the reversal of chemoresistance.

Linc2function: A Comprehensive Pipeline and Webserver for Long Non-Coding RNA (lncRNA) Identification and Functional Predictions Using Deep Learning Approaches.

Long non-coding RNAs (lncRNAs), comprising a significant portion of the human transcriptome, serve as vital regulators of cellular processes and potential disease biomarkers. However, the function of most lncRNAs remains unknown, and furthermore, existing approaches have focused on gene-level investigation. Our work emphasizes the importance of transcript-level annotation to uncover the roles of specific transcript isoforms. We propose that understanding the mechanisms of lncRNA in pathological processes requires solving their structural motifs and interactomes. A complete lncRNA annotation first involves discriminating them from their coding counterparts and then predicting their functional motifs and target bio-molecules. Current in silico methods mainly perform primary-sequence-based discrimination using a reference model, limiting their comprehensiveness and generalizability. We demonstrate that integrating secondary structure and interactome information, in addition to using transcript sequence, enables a comprehensive functional annotation. Annotating lncRNA for newly sequenced species is challenging due to inconsistencies in functional annotations, specialized computational techniques, limited accessibility to source code, and the shortcomings of reference-based methods for cross-species predictions. To address these challenges, we developed a pipeline for identifying and annotating transcript sequences at the isoform level. We demonstrate the effectiveness of the pipeline by comprehensively annotating the lncRNA associated with two specific disease groups. The source code of our pipeline is available under the MIT licensefor local use by researchers to make new predictions using the pre-trained models or to re-train models on new sequence datasets. Non-technical users can access the pipeline through a web server setup.

The emerging role of lncRNAs in osteoarthritis development and potential therapy.

Osteoarthritis impairs the functions of various joints, such as knees, hips, hands and spine, which causes pain, swelling, stiffness and reduced mobility in joints. Multiple factors, including age, joint injuries, obesity, and mechanical stress, could contribute to osteoarthritis development and progression. Evidence has demonstrated that genetics and epigenetics play a critical role in osteoarthritis initiation and progression. Noncoding RNAs (ncRNAs) have been revealed to participate in osteoarthritis development. In this review, we describe the pivotal functions and molecular mechanisms of numerous lncRNAs in osteoarthritis progression. We mention that long noncoding RNAs (lncRNAs) could be biomarkers for osteoarthritis diagnosis, prognosis and therapeutic targets. Moreover, we highlight the several compounds that alleviate osteoarthritis progression in part via targeting lncRNAs. Furthermore, we provide the future perspectives regarding the potential application of lncRNAs in diagnosis, treatment and prognosis of osteoarthritis.

Mesenchymal Stem Cell-Derived Long Noncoding RNAs in Cardiac Injury and Repair.

Cardiac injury, such as myocardial infarction and heart failure, remains a significant global health burden. The limited regenerative capacity of the adult heart poses a challenge for restoring its function after injury. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cardiac regeneration due to their ability to differentiate into various cell types and secrete bioactive molecules. In recent years, attention has been given to noncoding RNAs derived from MSCs, particularly long noncoding RNAs (lncRNAs), and their potential role in cardiac injury and repair. LncRNAs are RNA molecules that do not encode proteins but play critical roles in gene regulation and cellular responses including cardiac repair and regeneration. This review focused on MSC-derived lncRNAs and their implications in cardiac regeneration, including their effects on cardiac function, myocardial remodeling, cardiomyocyte injury, and angiogenesis. Understanding the molecular mechanisms of MSC-derived lncRNAs in cardiac injury and repair may contribute to the development of novel therapeutic strategies for treating cardiovascular diseases. However, further research is needed to fully elucidate the potential of MSC-derived lncRNAs and address the challenges in this field.