lncRNAs In Regulation Research Articles

Identification of regulatory genes associated with POAG by integrating expression and sequencing data

ABSTRACT Background Primary open-angle glaucoma (POAG) is a subtype of glaucoma that accounts for 60%~70% of all cases. Its pathogenic mechanism is intricate and its pathogenic process is concealed. Numerous significant biological processes associated with POAG continue to be elucidated. Methods In this study, by exploring the expression data of POAG tissues and normal tissues, we mined the regulatory lncRNAs and mRNAs closely associated with the pathogenesis and progression of POAG by exploring a regulatory network of competing endogenous RNA (ceRNA), established by integrating gene expression data with the known lncRNA–miRNA and miRNA–mRNA-regulatory interactions. The key regulatory pathways and regulatory elements of POAG were identified by topological analysis. Simultaneously, the exome data of 28 cases with POAG and healthy controls were analyzed to identify high-frequency mutations and genes. Results A total of 2712 differentially expressed genes were identified, including 1828 mRNAs and 884 lncRNAs. Network analysis suggested that lncRNAs such as HAGLR, HOTAIR and MIR29B2CHG, and mRNAs such as PPP6R3, BMPR2 and CFL2, may be involved in the onset and progression of POAG. In addition, 55 mutations with potential pathogenicity were identified. Conclusion These genes and mutations provide novel potential genetic heterogeneity and genetic susceptibility of POAG, as well as fresh suggestions for elucidating the molecular mechanism underlying the pathogenesis of POAG.

Metformin regulates the proliferation and motility of melanoma cells by modulating the LINC00094/miR-1270 axis.

Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear. We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays. We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher expression of LINC00094 in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissues (P < 0.001). In nondiabetic patients with melanoma, the overall survival of high LINC00094 expression group was shorter than the low LINC00094 expression group with borderline statistical significance (log-rank test, P = 0.057). Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that silencing-LINC00094 inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis following LINC00094 knockdown revealed G1 phase arrest with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Finally, through in silico analysis, we identified two miR-1270 target genes, CD276 and centromere protein M (CENPM), which may be involved in the biological functions of LINC00094. Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment.

Regulation and functions of long non-coding RNAs during Meloidogyne incognita parasitism of tomato.

Long non-coding RNAs (lncRNAs) are emerging as important regulators of various aspects of immune response and plant-pathogen interactions. However, the regulatory function of lncRNAs during plant-nematode interaction remain largely elusive. In this study, we investigated the differential regulation and function of lncRNAs during two different stages of tomato infection by the root-knot nematode Meloidogyne incognita. At the early stage of infection, 2218 and 2827 lncRNAs were regulated locally in the M. incognita-induced galls and systemically in the neighboring root cells, respectively. However, at the later stage of infection, the number of M. incognita-regulated lncRNAs was dramatically reduced with only 49 lncRNA being identified as differentially expressed. Differentially expressed lncRNAs were predicted to encode peptides with functionally annotated domains, providing insights into the potential roles of these peptides in regulating gene expression, RNA stability and splicing, and protein-protein-interactions. Among the differentially expressed lcRNAs, 55 were found to contain putative binding sites for 56 miRNAs. Overexpressing 5 of these lncRNAs significantly increased tomato resistance to M. incognita, supporting the functional importance of lncRNAs for establishing tomato-M. incognita interaction. Functional analysis of the target mimicry of lncRNAs towards miRNAs resulted in the identification of two novel regulatory modules involving miR47 and miR156e-5p and their targeted genes that regulate tomato responses to M. incognita parasitism. Taken together, our data provide novel insights into the transcriptional and post-transcriptional regulatory functions of lncRNA, and open a new avenue to engineer crop plants with enhanced nematode resistance by leveraging the regulatory potential of lncRNAs.

Mutations in the DNA processivity factor PCNA (POL30) predispose to epigenetic instability at the FLO11 locus

The FLO genes in S. cerevisiae are repressed by heterochromatin formation involving histone deacetylases, transcription factors, and non-coding RNAs. Here we report that mutations in processivity factor POL30 (PCNA) that show transient de-repression at the sub-telomeres and the mating-type loci, do not de-repress the FLO loci. However, deletions of the replisome-stability factors RRM3 and TOF1 along with pol30 mutations induce flocculation phenotypes. The phenotypes correlate with increased expression of reporter proteins driven by FLO11 promoter, the frequency of silent→active conversions of FLO11, and reduced expression of the regulatory lncRNAs ICR1 and PWR1. Alterations in the local replication landscape of FLO11 indicate a link between replication fork pausing and the stability of gene silencing. Analyses of these mutants at the sub-telomeres and HMLα show a similar de-repression phenotype and suggest transient instability of both active and silent states of FLO11. We conclude that RRM3 and TOF1 interact differentially with the pol30 mutations to promote transient de-repression or complete epigenetic conversions of FLO11. We suggest that interaction between POL30, RRM3, and TOF1 is essential to maintain epigenetic stability at the studied loci.

Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells.

Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation. We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis. More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation. We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation.

Identification of potential immune-related genes and infiltrations in temporomandibular joint osteoarthritis

Objective: The aim of this study was to investigate the potential inflammatory cytokines and chemokines markers for temporomandibular joint osteoarthritis (TMJOA) diagnosis using a bioinformatics analysis. Methods: The differentially expressed genes of mRNA (DEGs) and transcripts of lncRNA (DETs) were identified between TMJOA samples and normal controls curated from GSE205389 by the “DESeq. 2” R package. KEGG and GO were conducted using the R package “ggplot2” and “clusterProfiler”. A PPI network was constructed to identify hub genes by using the STRING and Cytoscape. The co-expression network was constructed between mRNA and lncRNA to check the potential regulation and function of lncRNA on protein coding genes. Finally, the immune cell infiltration analysis was conducted with CIBERSORTx and confirmed with xCells. Results: We identified 171 DEGs and DETs, of which the DEGs were closely related to immune response, T cell activation, cytokine-cytokine-receptor interaction, and the muscle system process. PPI network of the DEGs screened the top 10 hub genes, including IL6, IL1B, IL10, CCL2, CCL5, CXCL1, CXCL10, ICAM1, CSF1 and MMP1. Additionally, the immune cell infiltration analysis showed that CD8+ T cells, M1 macrophage and B cells infiltration were increased in TMJOA samples. Finally, we demonstrated that the co-expression between mRNA and lncRNA was mainly enriched in inflammatory and muscle related pathways. Conclusions: We found that immune and muscle system related pathways as well as the immune infiltration played a significant role in the TMJOA development. Additionally, inflammatory cytokines and chemokines could be crucial markers for early-stage TMJOA diagnosis and personalized treatment strategies.

LncPepAtlas: a comprehensive resource for exploring the translational landscape of long non-coding RNAs.

Long non-coding RNAs were commonly viewed as non-coding elements. However, they are increasingly recognized for their ability to be translated into proteins, thereby playing a significant role in various cellular processes and diseases. With developments in biotechnology and computational algorithms, a range of novel approaches are being applied to investigate the translation of long non-coding RNA (lncRNAs). Herein, we developed the LncPepAtlas database (http://www.cnitbiotool.net/LncPepAtlas/), which aims to compile multiple evidences for the translation of lncRNAs and annotations for the upstream regulation of lncRNAs across various species. LncPepAtlas integrated compelling evidence from nine distinct sources for the translation of lncRNAs. These include a dataset comprising 2631 publicly available Ribo-seq samples from nine species, which has been collected and analysed. LncPepAtlas offers extensive annotation for lncRNA upstream regulation and expression profiles across various cancers, tissues or cell lines at transcriptional and translational levels. Importantly, it enables novel antigen predictions for lncRNA-encoded peptides. By identifying numerous peptide candidates that could potentially bind to major histocompatibility complex class I and II molecules, this work may provide new insights into cancer immunotherapy. The function of peptides were inferred by aligning them with experimentally detected proteins. LncPepAtlas aims to become a convenient resource for exploring translatable lncRNAs.

Identification and functional characterization of lncRNAs involved in human monocyte-to-macrophage differentiation

ABSTRACT Although long noncoding RNAs (lncRNAs) constitute the majority of the human transcriptome, the functional roles of most remain elusive. While protein-coding genes in macrophage biology have been extensively studied, the contribution of lncRNAs in this context is poorly understood. Given the vast number of lncRNAs (>20,000), identifying candidates for functional characterization poses a significant challenge. Here, we present two complementary approaches to pinpoint and investigate lncRNAs involved in monocyte-to-macrophage differentiation: RNA-seq for functional inference and a high-throughput functional screen. These strategies enabled us to identify four lncRNA regulators of monocyte differentiation: lincRNA-JADE1, lincRNA-ANXA3, GATA2-AS1, and PPP2R5C-AS1. Preliminary insights suggest these lncRNAs may act in cis through neighbouring protein-coding genes, although their precise mechanisms remain to be elucidated. We further discuss the strengths and weaknesses of these methodologies, along with validation pipelines crucial for establishing lncRNA functionality.

Effects of Differentially Methylated CpG Sites in Enhancer and Promoter Regions on the Chromatin Structures of Target LncRNAs in Breast Cancer.

Aberrant DNA methylation plays a crucial role in breast cancer progression by regulating gene expression. However, the regulatory pattern of DNA methylation in long noncoding RNAs (lncRNAs) for breast cancer remains unclear. In this study, we integrated gene expression, DNA methylation, and clinical data from breast cancer patients included in The Cancer Genome Atlas (TCGA) database. We examined DNA methylation distribution across various lncRNA categories, revealing distinct methylation characteristics. Through genome-wide correlation analysis, we identified the CpG sites located in lncRNAs and the distally associated CpG sites of lncRNAs. Functional genome enrichment analysis, conducted through the integration of ENCODE ChIP-seq data, revealed that differentially methylated CpG sites (DMCs) in lncRNAs were mostly located in promoter regions, while distally associated DMCs primarily acted on enhancer regions. By integrating Hi-C data, we found that DMCs in enhancer and promoter regions were closely associated with the changes in three-dimensional chromatin structures by affecting the formation of enhancer-promoter loops. Furthermore, through Cox regression analysis and three machine learning models, we identified 11 key methylation-driven lncRNAs (DIO3OS, ELOVL2-AS1, MIAT, LINC00536, C9orf163, AC105398.1, LINC02178, MILIP, HID1-AS1, KCNH1-IT1, and TMEM220-AS1) that were associated with the survival of breast cancer patients and constructed a prognostic risk scoring model, which demonstrated strong prognostic performance. These findings enhance our understanding of DNA methylation's role in lncRNA regulation in breast cancer and provide potential biomarkers for diagnosis.

Comprehensive bioinformatics analysis of lncRNA regulation and screening for pathogenic genes in NF2-related schwannomatosis

Abstract Objectives NF2-related Schwannomatosis (NF2-SWN) is an autosomal dominant disease with full penetrance. Increasing data shows that long non-coding RNAs (lncRNA) can act as competitive endogenous RNAs (ceRNA), regulating target gene expression. This study aims to investigate lncRNAs in NF2-SWN that may be involved in regulating NF2 pathogenic genes. Methods Data were collected from three patients with NF2-SWN, including medical records, physical examination, imaging, pathology, and RNA from the tumor and adjacent tissues. differentially expressed genes (DEGs) between the two groups were screened by conducting gene differential analysis on the sequenced data. Next, GO &amp; KEGG enrichment analysis was performed on DEGs, and an association network between lncRNA and NF2 was established to identify regulatory lncRNA. Finally, qRT-PCR was used to substantiate the expression patterns of critical lncRNAs and NF2 in NF2-SWN. Results Sequencing revealed 6433 DEGs involved in key biological processes and pathways, such as axon guidance, intracellular signal transduction, cell migration, phosphorylation, cell adhesion molecules, taste transduction, axon guidance, and ErbB signaling pathways, etc. The ceRNA correlation network identified four lncRNAs (CADM3-AS1, MTMR9LP, LOC101929536, PRDM16-DT) that may regulate the NF2 gene. As expected, qRT-PCR results revealed that compared with the control group, the expression levels of L0C10929536 and PRDM16-DT in the tumor group were significantly increased. In contrast, the expression levels of MTMR9LP and CADM3-AS1 genes were decreased. Conclusions Four identified lncRNAs could be crucial for NF2-SWN development, potentially serving as diagnosis biomarkers or therapeutic targets. This study contributes to the understanding of NF2-SWN’s molecular mechanism.

N6-methyladenosine-modified lncRNA in Staphylococcus aureus-injured bovine mammary epithelial cells.

Staphylococcus aureus-induced mastitis is a serious disease in dairy bovine, with no currently effective treatment. Antibiotics demonstrate certain therapeutic potency in dairy husbandry; they generate drug-resistant bacteria, thereby harming public health. LncRNAs and m6A have been verified as potential targets in infectious diseases and have powerful regulatory capabilities. However, the biological regulation of lncRNAs with m6A modification in mastitis needs further investigation. This study aims to determine the m6A-modified lncRNAs in bovine mammary epithelial cells and their diversity during S. aureus induction. Heat-inactivated S. aureus was used to develop the cell injury model, and we subsequently found low cell viability and different m6A modification levels. Our analysis of m6A-modified lncRNA profiles through MeRIP-seq revealed significant differences in 140 peaks within 130 lncRNAs when cells were injured by S. aureus. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these differential m6A-modified lncRNAs were mainly enriched in the WNT pathway, and their functions were associated with amino acid metabolism, lipid translocation, and metalloproteinase activity. Here, we report for the first time lncRNAs with m6A modification in regulating S. aureus infection, revealing potential mechanisms and targets of infectious diseases, such as mastitis, from an epigenetics perspective.

Modelling cell type-specific lncRNA regulatory network in autism with Cycle

BackgroundAutism spectrum disorder (ASD) is a class of complex neurodevelopment disorders with high genetic heterogeneity. Long non-coding RNAs (lncRNAs) are vital regulators that perform specific functions within diverse cell types and play pivotal roles in neurological diseases including ASD. Therefore, exploring lncRNA regulation would contribute to deciphering ASD molecular mechanisms. Existing computational methods utilize bulk transcriptomics data to identify lncRNA regulation in all of samples, which could reveal the commonalities of lncRNA regulation in ASD, but ignore the specificity of lncRNA regulation across various cell types.ResultsHere, we present Cycle (Cell type-specificlncRNA regulatory network) to construct the landscape of cell type-specific lncRNA regulation in ASD. We have found that each ASD cell type is unique in lncRNA regulation, and more than one-third and all cell type-specific lncRNA regulatory networks are characterized as scale-free and small-world, respectively. Across 17 ASD cell types, we have discovered 19 rewired and 11 stable modules, along with eight rewired and three stable hubs within the constructed cell type-specific lncRNA regulatory networks. Enrichment analysis reveals that the discovered rewired and stable modules and hubs are closely related to ASD. Furthermore, more similar ASD cell types tend to be connected with higher strength in the constructed cell similarity network. Finally, the comparison results demonstrate that Cycle is a potential method for uncovering cell type-specific lncRNA regulation.ConclusionOverall, these results illustrate that Cycle is a promising method to model the landscape of cell type-specific lncRNA regulation, and provides insights into understanding the heterogeneity of lncRNA regulation between various ASD cell types.

Expression assays of selected lncRNAs in non-functioning pituitary adenomas

PurposeNon-functioning pituitary adenomas (NFPAs) are a group of these neoplasms originated from the adenohypophyse and do not show evidence of hormonal oversecretion. However, different genes and lncRNAs have been found to be dysregulated in these samples.Material and methodsIn this study, in order to identify novel biomarkers, a set of regulatory lncRNAs for the two important hub genes, i.e. STAT3 and EGFR were selected and subjected to experimental investigation. These lncRNAs were EGFR-AS1 for the EGFR gene, and LINC00240, FALEC and SNHG12 for the STAT3 gene.ResultsAll studied genes were down-regulated in NFPA samples compared with normal tissues adjacent to the tumors (NTATs), except for FALEC whose expression was not different between these two sets of samples. EGFR was the most significantly down-regulated gene in NFPAs (Expression ratio (95% CI) = 0.009 (0.002–0.04), P value < 0.0001). ROC curve analyses proposed that the expression levels of SNHG12, EGFR, EGFR-AS1 and LINC00240 can be used to distinguish NFPAs from NTATs with AUC values of 0.88, 0.83, 0.7 and 0.66, respectively. Spearman's correlation analyses showed significant correlations between FALEC and EGFR-AS1 in both types of tissues, and between FALEC and EGFR in NFPAs. Moreover, expression of LINC00240 was correlated with EGFR-AS1, FALEC and SNHG12 in NFPAs.ConclusionTaken together, EGFR and STAT3-related lncRNAs may be involved in the pathogenesis of NFPA.

Downregulation of Lnc-ABCA12-3 modulates UBQLN1 expression and protein homeostasis pathways in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration. Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in ALS pathogenesis but their roles remain unclear. Previous studies found lnc-ABCA12-3 was downregulated in ALS patients. We aim to characterize the expression and function of lnc-ABCA12-3 in ALS and explore its mechanisms of action. Lnc-ABCA12-3 expression was analyzed in PBMCs from ALS patients and correlated with clinical outcomes. Effect of modulating lnc-ABCA12-3 expression was assessed in cell models using assays of apoptosis, protein homeostasis and pathway analysis. RNA pull-down and interaction studies were performed to identify lnc-ABCA12-3 binding partners. Lnc-ABCA12-3 was downregulated in ALS patients, correlating with faster progression and shorter survival. Overexpression of lnc-ABAC12-3 conferred protection against oxidative stress-induced apoptosis, while knockdown lnc-ABCA12-3 enhanced cell death. Lnc-ABCA12-3 maintained protein quality control pathways, including ubiquitination, autophagy and stress granule formation, by regulating the ubiquitin shuttle protein UBQLN1. This study identified lnc-ABCA12-3 as a novel regulatory lncRNA implicated in ALS pathogenesis by modulating cellular survival and stress responses through interactions with UBQLN1, influencing disease progression. Lnc-ABCA12-3 may influence ALS through regulating protein homeostasis pathways.

Long Non-coding RNA DNM3OS: Pathogenic Roles and Molecular Mechanisms in Pathophysiological Processes.

Long non-coding RNA (lncRNA) is a class of single-stranded RNA biomolecules involving over 200 nucleotides and does not encode proteins. Research on lncRNA has become a hot spot for the past few years. DNM3OS (Dynamin 3 Opposite Strand), which has been clearly identified as a regulatory lncRNA, exerts an integral role in the pathophysiology of multiple human diseases. The current review study summarizes the pathogenic mechanism of DNM3OS in various pathophysiological processes, aiming to reveal its important value as a therapeutic drug target for related human diseases and provide a new way for targeted therapy. Through systematic retrieval and in-depth study of relevant articles in PubMed, this article analyzes and summarizes the pathogenic roles and molecular mechanisms in pathophysiological processes of long non-coding RNA DNM3OS. DNM3OS exerts an important regulatory role in the occurrence and development of bone diseases, neoplastic diseases, fibrotic diseases, inflammatory diseases, and many other diseases. DNM3OS is a potential new biomarker and therapeutic target for the treatment of a series of diseases, consisting of bone diseases, neoplastic diseases, fibrotic diseases, and inflammatory diseases.

Advances in understanding the role of lncRNA in ferroptosis.

LncRNA is a type of transcript with a length exceeding 200 nucleotides, which was once considered junk transcript with no biological function during the transcription process. In recent years, lncRNA has been shown to act as an important regulatory factor at multiple levels of gene expression, affecting various programmed cell death modes including ferroptosis. Ferroptosis, as a new form of programmed cell death, is characterized by a deficiency of cysteine or inactivation of glutathione peroxidase, leading to depletion of glutathione, aggregation of iron ions, and lipid peroxidation. These processes are influenced by many physiological processes, such as the Nrf2 pathway, autophagy, p53 pathway and so on. An increasing number of studies have shown that lncRNA can block the expression of specific molecules through decoy effect, guide specific proteins to function, or promote interactions between molecules as scaffolds. These modes of action regulate the expression of key factors in iron metabolism, lipid metabolism, and antioxidant metabolism through epigenetic or genetic regulation, thereby regulating the process of ferroptosis. In this review, we snapshotted the regulatory mechanism of ferroptosis as an example, emphasizing the regulation of lncRNA on these pathways, thereby helping to fully understand the evolution of ferroptosis in cell fate.

Porcine granulosa cell transcriptomic analyses reveal the differential regulation of lncRNAs and mRNAs in response to all-trans retinoic acid in vitro.

The active metabolite of vitamin A, all-trans retinoic acid (ATRA), is involved in the proliferation and differentiation of granulosa cells, and promotes the follicular development, oocyte maturation, and ovulation in mammals. This study aims to investigate the ATRA induced potential long noncoding RNAs (lncRNAs) that regulate the expression of genes associated with granulosa cell proliferation and follicular development. The lncRNA and mRNA profiles of porcine granulosa cells from ATRA treatment and control group in vitro were constructed through RNA sequencing. Meanwhile, the sequencing data were verified using quantitative polymerase chain reaction (qPCR). A total of 86 differentially expressed lncRNAs and 128 differentially expressed genes (DEGs) were detected in granulosa cells after ATRA treatment. The qRT-PCR results were consistent with the RNA-seq data. Functional annotation analysis revealed that the DEGs were remarkably enriched in ovary function and reproduction which contained FoxO, Hippo, Oocyte meiosis, mTOR signaling pathway, as well as several pathways associated with hormone regulation like Oxytocin signaling pathway and Steroid hormone biosynthesis. Moreover, an interaction network of lncRNAs and their cis-target DEGs was constructed, and 7 differentially expressed lncRNAs and 6 cis-target DEGs were enriched in ovarian steroidogenesis and reproduction. These findings expand the lncRNA catalogue and provide a basis for further studies on the mechanism of ATRA-mediated lncRNA regulation of follicular development in pigs.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer: From chemoresistance to autophagy

Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled “Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506” and “Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription” revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Screening for Genes Related to Meat Production Traits in Duroc × Bama Xiang Crossbred Pigs by Whole Transcriptome Sequencing.

The meat production traits of pigs are influenced by the expression regulation of multiple gene types, including mRNAs, miRNAs, and lncRNAs. To study the differences in meat production traits at the transcriptional level among individuals with different growth rates, the longissimus dorsi samples from eight Duroc × Bama Xiang F2 crossbred pigs with a fast growth rate (high gTroup) or a slow growth rate (low group) were selected to perform whole transcriptome sequencing and ceRNA regulatory network construction. This study first analyzed the differences in physiological and biochemical indicators, muscle histological characteristics, and muscle fiber types. A total of 248 mRNAs, 25 miRNAs, and 432 lncRNAs were identified as differentially expressed by whole transcriptome sequencing. Key genes that may influence meat production traits include MTMR14, PPP1R3A, PYGM, PGAM2, MYH1, and MYH7. The ceRNA regulatory network map showed that ENSSSCG00000042061-ssc-mir-208b-MYH7, ENSSSCG00000042223-ssc-mir-146a-MTMR14, ENSSSCG00000045539-ssc-mir-9-3-MYH1, and ENSSSCG00000047852-ssc-mir-103-1-PPP1R3A may be the key factors affecting meat production traits through their regulatory relationships. This study provides valuable insights into the molecular mechanisms underlying porcine muscle development and can aid in improving meat production traits.

Identification of RBM15 as a prognostic biomarker in prostate cancer involving the regulation of prognostic m6A-related lncRNAs

BackgroundLong noncoding RNAs (lncRNAs) and N6-methyladenosine (m6A) modification of RNA play pivotal roles in tumorigenesis and cancer progression. However, knowledge regarding the expression patterns of m6A-related lncRNAs and their corresponding m6A regulators in prostate cancer (PCa) is limited. This study aimed to delineate the landscape of m6A-related lncRNAs, develop a predictive model, and identify the critical m6A regulators of prognostic lncRNAs in PCa.MethodsClinical and transcriptome data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) database. Prognostic m6A-related lncRNAs were subsequently identified through Pearson correlation and univariate Cox regression analyses. The prognostic lncRNAs were clustered into two groups by consensus clustering analysis, and a risk signature model was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis of the lncRNAs. This model was evaluated using survival, clinicopathological, and immunological analyses. Furthermore, based on the constructed lncRNA-m6A regulatory network and RT-qPCR results, RBM15 was identified as a critical regulator of m6A-related lncRNAs. The biological roles of RBM15 in PCa were explored through bioinformatics analysis and biological experiments.ResultsThirty-four prognostic m6A-related lncRNAs were identified and categorized into two clusters with different expression patterns and survival outcomes in PCa patients. Seven m6A lncRNAs (AC105345.1, AL354989.1, AC138028.4, AC022211.1, AC020558.2, AC004076.2, and LINC02666) were selected to construct a risk signature with robust predictive ability for overall survival and were correlated with clinicopathological characteristics and the immune microenvironment of PCa patients. Among them, LINC02666 and AC022211.1 were regulated by RBM15. In addition, RBM15 expression correlated with PCa progression, survival, and the immune response. Patients with elevated RBM15 expression were more susceptible to the drug AMG-232. Moreover, silencing RBM15 decreased the viability of PCa cells and promoted apoptosis.ConclusionRBM15 is involved in the regulation of prognostic lncRNAs in the risk signature and has a robust predictive ability for PCa, making it a promising biomarker in PCa.