biostudies-literatureUnknown16Wan K<h4>Background</h4>Liver fibrosis (LF) represents a progressive pathophysiological consequence of persistent liver injury. Although the competitive endogenous RNA (ceRNA) network serves as a critical regulator in diverse disease pathogenesis, its molecular underpinnings in LF and fibrogenic mediators remain unknown.<h4>Objective</h4>In this study, we aimed to systematically probe the LF-related ceRNA regulatory axis and identify the potential molecules involved in the activation of hepatic stellate cells (HSCs).<h4>Methods and results</h4>Based on the whole transcriptome RNA sequencing, 401 lncRNAs, 60 miRNAs, and 1,224 mRNAs were identified between model and normal liver tissue samples. Then, through target gene prediction, an lncRNA-miRNA-mRNA (LMM) ceRNA network comprising four differentially expressed lncRNAs (DE lncRNAs), six DE miRNAs, and 148 DE mRNAs was established. The expression levels of these RNAs were verified by RT-qPCR. Functional annotation via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that target mRNAs of co-dysregulated lncRNAs and miRNAs in model groups were significantly enriched in multiple pathways, such as unsaturated fatty acids and TGF-β signaling pathways. Notably, four hub mRNAs (HMGCR, SREBF-1, TGF-β3, and FBN1) were identified by constructing a protein-protein interaction (PPI) network with the 148 DE mRNAs. Importantly, the dual-luciferase reporter assay confirmed the existence of specific binding sites among lncRNA H19, miR-148a-3p, and FBN1. Finally, the gene expression levels were verified by RT-qPCR in TGF-β1-induced JS-1 cells, revealing that five lncRNA-miRNA-mRNA relationship pairs containing H19, miR-130a-3p, miR-148a-3p, TGF-β3, FBN1, and HMGCR were involved in the activation of HSCs.<h4>Conclusion</h4>In this study, an HSC activation-related ceRNA network was successfully established in mice liver tissue, which could provide a novel framework for elucidating pathogenic mechanisms and identifying clinically relevant prognostic markers in LF progression.Frontiers in genetics1640326https://www.ebi.ac.uk/biostudies/studies/S-EPMC12640689biostudies-literatureConstruction of a HSC activation-related lncRNA-miRNA-mRNA ceRNA regulatory network reveals potential molecules involved in liver fibrosis.PMC12640689Li ZZhou QWan KFeng RLiu TPang XFan CfalseConstruction of a HSC activation-related lncRNA-miRNA-mRNA ceRNA regulatory network reveals potential molecules involved in liver fibrosis.<h4>Background</h4>Liver fibrosis (LF) represents a progressive pathophysiological consequence of persistent liver injury. Although the competitive endogenous RNA (ceRNA) network serves as a critical regulator in diverse disease pathogenesis, its molecular underpinnings in LF and fibrogenic mediators remain unknown.<h4>Objective</h4>In this study, we aimed to systematically probe the LF-related ceRNA regulatory axis and identify the potential molecules involved in the activation of hepatic stellate cells (HSCs).<h4>Methods and results</h4>Based on the whole transcriptome RNA sequencing, 401 lncRNAs, 60 miRNAs, and 1,224 mRNAs were identified between model and normal liver tissue samples. Then, through target gene prediction, an lncRNA-miRNA-mRNA (LMM) ceRNA network comprising four differentially expressed lncRNAs (DE lncRNAs), six DE miRNAs, and 148 DE mRNAs was established. The expression levels of these RNAs were verified by RT-qPCR. Functional annotation via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that target mRNAs of co-dysregulated lncRNAs and miRNAs in model groups were significantly enriched in multiple pathways, such as unsaturated fatty acids and TGF-β signaling pathways. Notably, four hub mRNAs (HMGCR, SREBF-1, TGF-β3, and FBN1) were identified by constructing a protein-protein interaction (PPI) network with the 148 DE mRNAs. Importantly, the dual-luciferase reporter assay confirmed the existence of specific binding sites among lncRNA H19, miR-148a-3p, and FBN1. Finally, the gene expression levels were verified by RT-qPCR in TGF-β1-induced JS-1 cells, revealing that five lncRNA-miRNA-mRNA relationship pairs containing H19, miR-130a-3p, miR-148a-3p, TGF-β3, FBN1, and HMGCR were involved in the activation of HSCs.<h4>Conclusion</h4>In this study, an HSC activation-related ceRNA network was successfully established in mice liver tissue, which could provide a novel framework for elucidating pathogenic mechanisms and identifying clinically relevant prognostic markers in LF progression.2025-01-01T00:00:00Z20252026-07-05T03:12:20.143Z2026-07-05T03:08:29.7ZS-EPMC126406894128779110.3389/fgene.2025.1640326