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Keywords = lncRNA-mRNA association analysis

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17 pages, 4009 KiB  
Article
Investigation of the Impact of miRNA-7151 and a Mutation in Its Target Gene lncRNA KCNQ1OT1 on the Pathogenesis of Preeclampsia
by Wuqian Wang, Xiaojia Wu, Jianmei Gu, Luan Chen, Weihua Zhang, Xiaofang Sun, Shengying Qin and Ping Tang
Biomedicines 2025, 13(8), 1813; https://doi.org/10.3390/biomedicines13081813 - 24 Jul 2025
Viewed by 312
Abstract
Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between [...] Read more.
Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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19 pages, 3656 KiB  
Article
Large-Scale Profiling of Coding and Long Noncoding Transcriptomes in the Hippocampus of Mice Acutely Exposed to Vaporized CBD or THC
by Mi Ran Choi, Jihun Kim, Chaeeun Park, Seok Hwan Chang, Han-Na Kim, Yeung Bae Jin and Sang-Rae Lee
Int. J. Mol. Sci. 2025, 26(15), 7106; https://doi.org/10.3390/ijms26157106 - 23 Jul 2025
Viewed by 236
Abstract
Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or [...] Read more.
Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs—including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2—were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA–mRNA interactions in cannabinoid-induced neural changes. Full article
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30 pages, 8781 KiB  
Article
RNA-Seq Analysis of Mouse Hepatocytes AML12 Exposed to Neodymium Nitrate
by Ning Wang, Jing Leng, Yaxin Han, Gonghua Tao, Jingqiu Sun, Cheng Dong, Kelei Qian, Xiuli Chang, Ping Xiao and Xinyu Hong
Toxics 2025, 13(7), 573; https://doi.org/10.3390/toxics13070573 - 7 Jul 2025
Viewed by 484
Abstract
Objective: Neodymium nitrate (Nd(NO3)3) is widely used globally, raising concerns about its occupational and environmental safety. It enters the human body via the digestive system, accumulates in organs, and causes toxicity, including potential hepatotoxicity. However, the role of non-coding [...] Read more.
Objective: Neodymium nitrate (Nd(NO3)3) is widely used globally, raising concerns about its occupational and environmental safety. It enters the human body via the digestive system, accumulates in organs, and causes toxicity, including potential hepatotoxicity. However, the role of non-coding RNAs (ncRNAs) in Nd(NO3)3-induced liver injury remains unclear. This study aimed to identify key genes and regulatory pathways involved in Nd(NO3)3-induced hepatic injury using RNA sequencing (RNA-seq) and differential gene expression analysis. Methods: Mouse hepatocytes (AML12 cells) were exposed to Nd(NO3)3, and RNA-seq was performed to analyze the expression profiles of miRNA, lncRNA, circRNA, and mRNA. qPCR was used to validate the RNA-seq results. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functions and pathways associated with differentially expressed genes (DEGs). Results: Nd(NO3)3 exposure altered the expression of ferroptosis-related genes and induced significant changes in mRNA, miRNA, circRNA, and lncRNA expression levels. GO and KEGG analyses revealed that DEGs were closely related to cellular ferroptosis pathways. Specific miRNAs, lncRNAs, and circRNAs were significantly upregulated, suggesting their potential as biomarkers for Nd(NO3)3-induced ferroptosis and liver injury. Conclusion: This study provides the first comprehensive transcriptome database for Nd(NO3)3-induced liver injury, highlighting the involvement of ncRNAs in hepatotoxicity. These findings offer valuable insights for developing biomarkers and understanding the mechanisms underlying Nd(NO3)3-induced hepatic injury. Full article
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35 pages, 15694 KiB  
Article
Regulatory RNA Networks in Ovarian Follicular Cysts in Dairy Cows: Implications for Human Polycystic Ovary Syndrome
by Ramanathan Kasimanickam, Vanmathy Kasimanickam, Joao Ferreira, John Kastelic and Fabiana de Souza
Genes 2025, 16(7), 791; https://doi.org/10.3390/genes16070791 - 30 Jun 2025
Viewed by 426
Abstract
Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling [...] Read more.
Background/Objectives: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. Methods: Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein–protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). Results: Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. Conclusions: The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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15 pages, 2076 KiB  
Article
Validation of Targeted Relationships of Novel circRNA803/lncRNA MSTRG.19726–oar-let-7a–CPEB1 ceRNA Networks, Key to Follicle Development in Single-Litter and Multi-Litter Sheep Based on Whole-Transcriptome Sequencing
by Bo Gu, Anqi Wang, Hang Liu, Xudong Liu and Huaizhi Jiang
Int. J. Mol. Sci. 2025, 26(11), 5161; https://doi.org/10.3390/ijms26115161 - 28 May 2025
Viewed by 401
Abstract
The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter [...] Read more.
The objective of this study is to investigate the molecular regulatory mechanisms of non-coding RNA (ncRNA) during the developmental process of multi-litter sheep ovaries and identify key regulatory genes that enhance the reproductive capacity of sheep. This study selected Small-Tail Han sheep (multi-litter sheep) and Ujumuqin sheep (single-litter sheep) as comparative models, constructed the expression profiles of ncRNAs and mRNAs in ovarian tissues, identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and performed target gene prediction along with functional and signaling pathway enrichment analyses. Reproduction-related pathways were further screened to construct competing endogenous RNA (ceRNA) regulatory networks (lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA). Finally, the dual-luciferase reporter gene assay system was employed to perform the functional validation of the relevant targeted regulatory effects. A comprehensive screening identified 411 DE lncRNAs, 322 DE circRNAs, 26 DE miRNAs, and 29 DEGs from the ovarian tissues of Ujumqin and Small-Tail Han sheep. The results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that the DE target genes were significantly enriched in pathways associated with cell dedifferentiation, the positive regulation of embryonic development, glycosaminoglycan biosynthesis, Hippo signaling, and other signaling pathways. To identify genes associated with reproductive processes, we performed differential expression screening followed by pathway enrichment analysis, which revealed significant enrichment in reproductive regulatory pathways. Based on these findings, we constructed a ceRNA regulatory network incorporating 22 DEGs, 17 DE lncRNAs, three DE circRNAs, and one DE miRNA. Our analysis revealed that oar-let-7a is involved in signaling pathways such as oocyte meiosis and Hippo, suggesting it may serve as a key miRNA regulating the trait of multiple offspring. The dual-luciferase reporter assay was employed to confirm that oar-let-7a directly targets and regulates the expression of CPEB1. Additionally, it was demonstrated that circRNA803 and lncRNA MSTRG.19726 function as molecular sponges to competitively bind and regulate oar-let-7a. These findings suggest that oar-let-7a mediates the expression of CPEB1 via circRNA803 and lncRNA MSTRG.19726 sponge adsorption, thereby regulating the process of follicular dominance in sheep. The qRT-PCR method was employed to validate the expression patterns of nine randomly selected DEGs, and the results corroborated the reliability of the RNA-seq sequencing data. This study investigated the coordinated regulatory mechanism of DE ncRNAs and their corresponding target genes, identifying a ceRNA network, circRNA803/lncRNA MSTRG.19726-oar-let-7a-CPEB1, which plays a critical role in regulating the process of follicular dominance in sheep. These findings provide fundamental data for uncovering the reproductive potential of sheep and facilitate a comprehensive understanding of their reproductive characteristics, which hold significant guiding implications for enhancing reproductive efficiency. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 5621 KiB  
Article
Differential Expression of lncRNAs in Ovarian Tissue of Meigu Goats During the Sexually Immature and Mature Periods
by Juntao Li, Yanan Xue, Tao Zhong, Linjie Wang, Li Li, Hongping Zhang and Siyuan Zhan
Curr. Issues Mol. Biol. 2025, 47(6), 395; https://doi.org/10.3390/cimb47060395 - 26 May 2025
Viewed by 419
Abstract
The ovary is the primary reproductive organ in goats, and its development significantly influences the sexual maturity and reproductive capacity of individuals. Long non-coding RNAs (lncRNAs) are integral to a wide array of biological processes. However, the regulatory function of lncRNAs in the [...] Read more.
The ovary is the primary reproductive organ in goats, and its development significantly influences the sexual maturity and reproductive capacity of individuals. Long non-coding RNAs (lncRNAs) are integral to a wide array of biological processes. However, the regulatory function of lncRNAs in the development of ovarian tissue during sexual maturity in goats remains largely unexplored. In this study, we conducted RNA sequencing on ovarian tissue samples from Meigu goats at sexually immature (3 months, n = 3) and sexually mature periods (6 months, n = 3). We identified a total of 966 lncRNAs across six libraries, with 95 lncRNAs exhibiting differential expression. Additionally, we identified the target genes of these DElncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these target genes were associated with various biological processes and pathways pertinent to ovarian development, including reproduction, reproductive process, JAK-STAT signaling pathway, progesterone-mediated oocyte maturation, Wnt signaling pathway, and cytokine–cytokine receptor interaction. Furthermore, lncRNA–mRNA interaction network analysis suggested that MSTRG.15120.9 and MSTRG.15110.2 play crucial regulatory roles in ovarian development. This study provides a valuable resource for elucidating the molecular regulatory mechanisms of lncRNAs in ovarian tissue during the sexual maturity period in goats. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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17 pages, 3624 KiB  
Article
Competitive Endogenous RNA Network Involving Immune Subgroups, Infiltration, and lncRNAs in Prostate Cancer
by Wenkang Niu, Tingting Zhang and Lei Ma
Genes 2025, 16(5), 527; https://doi.org/10.3390/genes16050527 - 29 Apr 2025
Viewed by 602
Abstract
Prostate cancer (PCa) is the most frequently diagnosed malignancy in the male genitourinary tract. However, the regulatory mechanism of competitive endogenous RNAs (ceRNAs) in PCa remains unclear. In this study, we first performed immune scores of mRNA data from 481 PCa samples using [...] Read more.
Prostate cancer (PCa) is the most frequently diagnosed malignancy in the male genitourinary tract. However, the regulatory mechanism of competitive endogenous RNAs (ceRNAs) in PCa remains unclear. In this study, we first performed immune scores of mRNA data from 481 PCa samples using single-sample Gene Set Enrichment Analysis (ssGSEA). Based on the immune scores, we then evaluated the tumor immune microenvironment and analyzed 28 types of immune cells in PCa, we constructed a comprehensive network with four lncRNAs (MEG3, PCAT1, SNHG19, TRG-AS1), three miRNAs (hsa-miR-488-3p, hsa-miR-210-5p, hsa-miR-137), and twenty-seven mRNAs (including H2AFJ, THBS1, HPGD). Among the 28 immune cell types, seven immune cell types were found to be significantly associated with clinical characteristics. These network nodes have prognostic significance in multiple cancers and play critical roles in malignancy development, indicating the network’s predictive capability. We also observed a strong correlation (r = 0.6) between T-helper type 1 (Th1) cells and lncRNA network modules. The network connectivity highlights the association between immune therapy biomarkers for PCa, particularly those related to H2AFJ, THBS1, and HPGD. These findings provide valuable insights into the ceRNA regulatory network and its implications for immune-based therapies in PCa. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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15 pages, 3366 KiB  
Article
Long Non-Coding RNA lncXIRP1 Regulates the Proliferation and Apoptosis of Pig Leydig Cells
by Haiyan Yang, Xianzhao Lu, Shan Zhang, Qi Tang, Xianyong Lan, Jing Wang, Xiaolei Chen and Chuanying Pan
Agriculture 2025, 15(8), 802; https://doi.org/10.3390/agriculture15080802 - 8 Apr 2025
Viewed by 483
Abstract
Leydig cells (LCs) originate from stem Leydig cells (SLCs) and synthesize testosterone, a hormone indispensable for the development, sustenance, and functionality of the male reproductive system. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play pivotal roles in animal reproductive processes, yet the [...] Read more.
Leydig cells (LCs) originate from stem Leydig cells (SLCs) and synthesize testosterone, a hormone indispensable for the development, sustenance, and functionality of the male reproductive system. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play pivotal roles in animal reproductive processes, yet the functional contributions of lncRNAs in pig LCs remain largely uncharacterized. The aim of this study was to examine how lncRNAs influence the function of LCs and their underlying molecular regulatory mechanisms. To achieve this, RNA-seq was conducted on cells before ethane dimethane sulfonate (EDS) treatment (SLCs and LCs) and after EDS treatment (SLCs), identifying 887 significantly downregulated lncRNAs and 30 upregulated lncRNAs after EDS treatment. Bioinformatics analysis identified lncXIRP1 for further investigation. The effects of lncXIRP1 on LCs proliferation, apoptosis, and expression of genes related to testosterone synthesis were investigated by using RT-qPCR, Western blot, CCK-8 and other methods. Bioinformatics predictions have unveiled the existence of a binding site between lncXIRP1 and IGFBP3. Through RT-qPCR experiments and a dual-luciferase reporter system, it was conclusively demonstrated that lncXIRP1 has the capacity to repress the expression of IGFBP3 mRNA, thereby inhibiting the proliferation and transcription activity of genes associated with testosterone synthesis in LCs and promoting their apoptosis. These results provide a theoretical foundation for further exploration of the impact of lncRNAs on LCs function and improving pig reproductive performance. Full article
(This article belongs to the Section Farm Animal Production)
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25 pages, 3357 KiB  
Review
Clinical Significance of LINC00261 in the Pathogenesis of Pancreatic, Colorectal, Hepatocellular, and Gallbladder Cancer
by Sanjana Bana, Sia Daffara, Aastha Dagar, Ashutosh Kumar Tiwari, Kanupriya Medhi, Sagarika Mukherjee, Vivek Uttam, Md Rizwan Ansari, Hardeep Singh Tuli, Vikas Yadav and Aklank Jain
Diseases 2025, 13(3), 89; https://doi.org/10.3390/diseases13030089 - 20 Mar 2025
Cited by 1 | Viewed by 790
Abstract
Pancreatic (PC), colorectal (CRC), hepatocellular (HCC), and gallbladder (GC) cancers together account for nearly 20% of all cancer cases. However, specific biomarkers and therapeutic targets for these cancers are lacking. Diagnosing these cancers early and providing timely, appropriate treatment to improve patient outcomes [...] Read more.
Pancreatic (PC), colorectal (CRC), hepatocellular (HCC), and gallbladder (GC) cancers together account for nearly 20% of all cancer cases. However, specific biomarkers and therapeutic targets for these cancers are lacking. Diagnosing these cancers early and providing timely, appropriate treatment to improve patient outcomes is crucial. In this context, previous studies, including ours, have highlighted the potential of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in diagnosing and prognosis of various cancers. This review focuses on the mechanistic role of the recently identified lncRNA LINC00261 in PC, CRC, HCC, and GC. Our comprehensive literature analysis revealed that LINC00261 functions as a tumor suppressor, and its reduced expression is associated with larger tumor size, advanced tumor-node-metastasis (TNM) stages, lymphatic metastasis, and poorer overall survival rates. Additionally, we discovered that LINC00261 acts as a molecular sponge for miRNAs, such as miR-550a-3p, miR-23a-3p, miR-148a, miR-324-3p, and miR-105-5p, regulating critical cancer-related signaling pathways, including PI3K/Akt/mTOR, Protein kinase B, and Mammalian target of rapamycin (mTOR). Further bioinformatic analysis revealed that LINC00261 regulates key cellular processes, such as protein-DNA complex formation, ribonuclease complex activity, histone deacetylase complexes, and nuclear matrix interactions. Overall, we believe that LINC00261 holds significant promise as a future biomarker and, when combined with existing treatment strategies, may enhance cancer patient care and survival. Full article
(This article belongs to the Section Oncology)
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18 pages, 4146 KiB  
Article
Identification and Assessment of lncRNAs and mRNAs in PM2.5-Induced Hepatic Steatosis
by Peixuan Tian, Hui Xia, Xinbao Li, Ying Wang, Bihuan Hu, Yu Yang, Guiju Sun and Jing Sui
Int. J. Mol. Sci. 2025, 26(6), 2808; https://doi.org/10.3390/ijms26062808 - 20 Mar 2025
Cited by 1 | Viewed by 780
Abstract
Research indicates that fine particulate matter (PM2.5) exposure is associated with the onset of non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disorder. However, the underlying pathogenesis mechanisms remain to be fully understood. Our study investigated the hub long non-coding RNAs [...] Read more.
Research indicates that fine particulate matter (PM2.5) exposure is associated with the onset of non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disorder. However, the underlying pathogenesis mechanisms remain to be fully understood. Our study investigated the hub long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) associated with hepatic steatosis caused by PM2.5 exposure and their pathological mechanisms. The analysis of gene profiles in the GSE186900 dataset from the Gene Expression Omnibus (GEO) enabled the identification of 38 differentially expressed lncRNAs and 1945 mRNAs. To explore further, a co-expression network was established utilizing weighted gene co-expression network analysis (WGCNA). Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. Our analysis identified specific modules, particularly the blue and turquoise modules, which showed a strong correlation with NAFLD. Through functional enrichment analysis, we identified several lncRNAs (including Gm15446, Tmem181b-ps, Adh6-ps1, Gm5848, Zfp141, Rmrp, and Rb1) which may be involved in modulating NAFLD, multiple metabolic pathways, inflammation, cell senescence, apoptosis, oxidative stress, and various signaling pathways. The hub lncRNAs identified in our study provide novel biomarkers and potential targets for the diagnosis and treatment of NAFLD. Full article
(This article belongs to the Special Issue Chronic Liver Disease: From Pathophysiology to Treatment)
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34 pages, 5820 KiB  
Article
Identification of Genomic Instability-Associated LncRNAs as Potential Therapeutic Targets in Lung Adenocarcinoma
by Vanessa G. P. Souza, Katya H. Benard, Greg L. Stewart, Katey S. S. Enfield and Wan L. Lam
Cancers 2025, 17(6), 996; https://doi.org/10.3390/cancers17060996 - 15 Mar 2025
Viewed by 1188
Abstract
Background/Objectives: Non-small cell lung cancer (NSCLC) is the most common type of cancer, with lung adenocarcinoma (LUAD) as the predominant subtype. Despite advancements in targeted therapies, many NSCLC patients still experience poor outcomes due to treatment resistance and disease progression. Genomic instability (GI), [...] Read more.
Background/Objectives: Non-small cell lung cancer (NSCLC) is the most common type of cancer, with lung adenocarcinoma (LUAD) as the predominant subtype. Despite advancements in targeted therapies, many NSCLC patients still experience poor outcomes due to treatment resistance and disease progression. Genomic instability (GI), a hallmark of cancer, defined as the increased tendency of DNA mutations and alterations, is closely linked to cancer initiation, progression, and resistance to therapy. Emerging evidence suggests that long non-coding RNAs (lncRNAs)—molecules longer than 200 nucleotides that do not encode proteins but regulate gene expression—play critical roles in cancer biology and are associated with GI. However, the relationship between GI and lncRNA expression in LUAD remains poorly understood. Methods: In this study, we analyzed the transcript profiles of lncRNAs and mRNAs from LUAD samples in The Cancer Genome Atlas (TCGA) database and classified them based on their Homologous Recombination Deficiency (HRD) score. The HRD score is an unweighted sum of three independent DNA-based measures of genomic instability: loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions. We then performed a differential gene expression analysis to identify lncRNAs and mRNAs that were either upregulated or downregulated in samples with high HRD scores compared to those with low HRD scores. Following this, we conducted a correlation analysis to assess the significance of the association between HRD scores and the expression of both lncRNAs and mRNAs. Results: We identified 30 differentially expressed lncRNAs and 200 mRNAs associated with genomic instability. Using an RNA interactome database from sequencing experiments, we found evidence of interactions between GI-associated lncRNAs (GI-lncRNAs) and GI-associated mRNAs (GI-mRNAs). Further investigation showed that some GI-lncRNAs play regulatory and functional roles in LUAD and other diseases. We also found that GI-lncRNAs have potential as prognostic biomarkers, particularly when integrated with HRD stratification. The expression of specific GI-lncRNAs was associated with primary therapy response and immune infiltration in LUAD. Additionally, we identified existing drugs that could modulate GI-lncRNAs, offering potential therapeutic strategies to address GI in LUAD. Conclusions: Our findings suggest that GI-associated lncRNAs could serve as valuable biomarkers for LUAD prognosis and therapeutic response. Furthermore, modulating these lncRNAs presents potential treatment avenues to address genomic instability in LUAD. Full article
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16 pages, 3532 KiB  
Article
Hypothalamus Transcriptome Reveals Key lncRNAs and mRNAs Associated with Fecundity in Goats
by Yingshi Wei, Caiye Zhu, Xiaoyun He and Mingxing Chu
Animals 2025, 15(5), 754; https://doi.org/10.3390/ani15050754 - 6 Mar 2025
Viewed by 763
Abstract
The hypothalamus (hyp) serves as the regulatory hub of the neuroendocrine system, synthesizing and secreting reproductive hormones that modulate estrus, follicular maturation, and embryonic development in goats. This study employed RNA-seq analysis to examine gene expression in the hypothalamic tissue of Yunshang black [...] Read more.
The hypothalamus (hyp) serves as the regulatory hub of the neuroendocrine system, synthesizing and secreting reproductive hormones that modulate estrus, follicular maturation, and embryonic development in goats. This study employed RNA-seq analysis to examine gene expression in the hypothalamic tissue of Yunshang black goats during the luteal phase in goats with high fecundity (LP_HY), during the luteal phase in goats with low fecundity (LP_LY), during the follicular phase in goats with high fecundity (FP_HY), and during the follicular phase in goats with low fecundity (FP_LY). Differential long non-coding RNAs (DE lncRNAs) and differential mRNAs (DE mRNAs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and the construction of co-expression networks associated with reproduction. As a result, DE lncRNAs (390, 375, 405, and 394) and DE mRNAs (1836, 2047, 2003, and 1963) were identified in the four comparisons, namely FP_LY vs. FP_HY, LP_HY vs. FP_HY, LP_LY vs. FP_LY, and LP_LY vs. LP_HY, respectively. Functional annotations indicated significant enrichment of numerous DE lncRNAs and DE mRNAs in reproduction-related pathways such as the gonadotropin-releasing hormone pathway, the prolactin signaling pathway, the estrogen signaling pathway, the Wnt signaling pathway, oocyte meiosis, and progesterone-mediated oocyte maturation. The co-expression network of lncRNAs and target genes identified the interrelationships between reproduction-related genes such as IGF1, PORCN, PLCB2, MAPK8, PRLR, and CPEB2 with our newly discovered lncRNAs. This study expands the understanding of lncRNAs and mRNAs in goat hypothalamic tissue and provides new insights into molecular mechanisms related to goat reproduction. Full article
(This article belongs to the Section Small Ruminants)
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21 pages, 7423 KiB  
Article
Cytosolic and Nucleosolic Calcium-Regulated Long Non-Coding RNAs and Their Target Protein-Coding Genes in Response to Hyperosmolarity and Salt Stresses in Arabidopsis thaliana
by Doudou Wang, Kaifeng Zheng, Wenfen Long, Liang Zhao, Wanjie Li, Xiuhua Xue and Shengcheng Han
Int. J. Mol. Sci. 2025, 26(5), 2086; https://doi.org/10.3390/ijms26052086 - 27 Feb 2025
Cited by 1 | Viewed by 643
Abstract
Long non-coding RNAs (lncRNAs) are involved in plant biotic and abiotic stress responses, in which Ca2+ also plays a significant role. There is diversity in the regulation of different gene expressions by cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic [...] Read more.
Long non-coding RNAs (lncRNAs) are involved in plant biotic and abiotic stress responses, in which Ca2+ also plays a significant role. There is diversity in the regulation of different gene expressions by cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc). However, no studies have yet explored the interrelationship between lncRNAs and calcium signaling, nor how calcium signaling regulates the expression of lncRNAs. Here, we use transgenic materials PV-NES and NLS-PV, which simulate [Ca2+]cyt- and [Ca2+]nuc-deficient mutants, respectively, and wild type (WT) materials in response to hyperosmolarity (250 mM sorbitol) or salt stresses (125 mM NaCl) at different time points to obtain RNA-seq data, respectively. Then, we proceed with the screening of lncRNAs, adding 688 new lncRNAs to the known Arabidopsis lncRNA database. Subsequently, through the analysis of differentially expressed lncRNA genes, it was found that cytosolic or nucleosolic calcium signals have distinct regulatory effects on differentially expressed lncRNAs (DElncRNAs) and differentially expressed protein-coding genes (DEPCGs) treated with high-concentration NaCl and sorbitol at different times. Furthermore, through weighted correlation network analysis (WGCNA), it is discovered that under hyperosmolarity and salt stresses, lncRNA-associated PCGs are related to the cell wall structure, the plasma membrane component, and osmotic substances through trans-regulation. In addition, by screening for cis-regulatory target PCGs of Ca2+-regulated lncRNAs related to osmotic stress, we obtain a series of lncRNA-PCG pairs related to water transport, cell wall components, and lateral root formation. Therefore, we expand the existing Arabidopsis lncRNA database and obtain a series of lncRNAs and PCGs regulated by [Ca2+]cyt or [Ca2+]nuc in response to salt and hyperosmolarity stress, providing a new perspective for subsequent research on lncRNAs. We also explore the trans- and cis-regulated target PCGs of lncRNAs regulated by calcium signaling, providing new insights for further studying salt stress and osmotic stress. Full article
(This article belongs to the Special Issue Advanced Plant Molecular Responses to Abiotic Stresses)
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28 pages, 3134 KiB  
Article
Identification and Network Construction of mRNAs, miRNAs, lncRNAs, and circRNAs in Sweetpotato (Ipomoea batatas L.) Adventitious Roots Under Salt Stress via Whole-Transcriptome RNA Sequencing
by Bo Jiang, Yuxia Li, Jun Shi, Dagaga Dibaba Chalasa, Lei Zhang, Shaoyuan Wu and Tao Xu
Int. J. Mol. Sci. 2025, 26(4), 1660; https://doi.org/10.3390/ijms26041660 - 15 Feb 2025
Cited by 1 | Viewed by 1133
Abstract
Sweetpotato is the seventh largest crop worldwide, and soil salinization is a major environmental stress limiting its yield. Recent studies have shown that noncoding RNAs (ncRNAs) play important regulatory roles in plant responses to abiotic stress. However, ncRNAs in sweetpotato remain largely unexplored. [...] Read more.
Sweetpotato is the seventh largest crop worldwide, and soil salinization is a major environmental stress limiting its yield. Recent studies have shown that noncoding RNAs (ncRNAs) play important regulatory roles in plant responses to abiotic stress. However, ncRNAs in sweetpotato remain largely unexplored. This study analyzed the characteristics of salt-responsive ncRNAs in sweetpotato adventitious roots under salt stress via whole-transcriptome RNA sequencing. The results revealed that 3175 messenger RNAs (mRNAs), 458 microRNAs (miRNAs), 544 long-chain ncRNAs (lncRNAs), and 23 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that most differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were enriched primarily in phenylpropanoid biosynthesis, starch and sucrose metabolism, the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, plant hormone signal transduction, the mRNA surveillance pathway, and ATP-binding cassette (ABC) transporters. Gene Ontology (GO) enrichment analysis revealed that the majority of DEmRNAs, their target DEmiRNAs, and differentially expressed lncRNAs (DElncRNAs) were associated with the cell wall, oxidation–reduction, the plasma membrane, protein phosphorylation, metabolic processes, transcription factor activity, and the regulation of transcription. Additionally, based on the competitive endogenous RNA (ceRNA) hypothesis, we predicted interactions among different RNAs and constructed a salt-responsive ceRNA network comprising 22 DEmiRNAs, 42 DEmRNAs, 27 DElncRNAs, and 10 differentially expressed circRNAs (DEcircRNAs). Some miRNAs, such as miR408, miR169, miR160, miR5139, miR5368, and miR6179, were central to the network, suggesting their crucial roles in the sweetpotato salt response. Our findings provide a foundation for further research into the potential functions of ncRNAs and offer new targets for salt stress resistance improvement through the manipulation of ncRNAs. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Plant Abiotic Stress Tolerance: 2nd Edition)
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23 pages, 12494 KiB  
Article
Identifying Essential Hub Genes and circRNA-Regulated ceRNA Networks in Hepatocellular Carcinoma
by Xiaoqian Yu, Hao Xu, Yutao Xing, Dehui Sun, Dangdang Li, Jinming Shi, Guangchao Sui and Guangyue Li
Int. J. Mol. Sci. 2025, 26(4), 1408; https://doi.org/10.3390/ijms26041408 - 7 Feb 2025
Viewed by 1283
Abstract
Competitive endogenous RNAs (ceRNAs) absorb microRNAs and subsequently promote corresponding mRNA and long noncoding RNA (lncRNA) expression, which may alter cancer cell malignancy. Thus, dissecting ceRNA networks may reveal novel targets in cancer therapies. In this study, we analyzed differentially expressed genes (DEGs) [...] Read more.
Competitive endogenous RNAs (ceRNAs) absorb microRNAs and subsequently promote corresponding mRNA and long noncoding RNA (lncRNA) expression, which may alter cancer cell malignancy. Thus, dissecting ceRNA networks may reveal novel targets in cancer therapies. In this study, we analyzed differentially expressed genes (DEGs) of mRNAs and lncRNAs, and differentially expressed microRNAs (DE-miRNAs) and circular RNAs (DE-circRNAs) extracted from high-throughput sequencing datasets of hepatocellular carcinoma patients. Based on these data, we identified 26 gene modules using weighted gene co-expression network analysis (WGCNA), of which 5 were associated with tumor differentiation. In these modules, 269 genes were identified by GO and KEGG enrichment and patient’s survival correlation analyses. Next, 40 DE-miRNAs, each of which potentially bound a pair of DE-circRNA and hub gene, were discovered. Together with 201 circRNAs and 24 hub genes potentially bound by these miRNAs, 1151 ceRNA networks were constructed. Among them, 75 ceRNA networks consisting of 24 circRNAs, 28 miRNAs and 17 hub genes showed a positive circRNA–hub gene correlation. For validation, we carried out experiments for 4 randomly selected circRNAs regulating 19 potential ceRNA networks and verified 5 of them. This study represents a powerful strategy to identify essential gene networks and provides insights into designing effective therapeutic strategies. Full article
(This article belongs to the Special Issue Regulation by Non-Coding RNAs 2025)
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