Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, Changsha, 410008, People's Republic of China.
BMC Med Genomics. 2024 Feb 20;17(1):56. doi: 10.1186/s12920-024-01813-x.
Liver fibrosis is a major global healths problem; nevertheless, its molecular mechanism are not completely clear. This study aimed to build a lncRNA-miRNA-mRNA network, identify potentially related lncRNAs, and explore the pathogenesis of liver fibrosis.
We used the Gene Expression Omnibus databases and bioinformatics analysis to identify differentially expressed genes (DEGs) between liver fibrosis and normal tissues. The ceRNA network was constructed according to the interactions between DElncRNA, miRNA, and DEmRNA. Then, these DEGs were identified using functional enrichment analysis, and a protein-protein interaction (PPI) network was established. The critical lncRNAs were verified using the quantitative real-time polymerase chain reaction (qRT-PCR).
The ceRNA network was composed of three lncRNAs, five miRNAs, and 93 mRNAs. Gene Ontology functional enrichment analysis revealed significant enhancement in cell components, molecular function, and biological process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed pathways associated with transcriptional misregulation in cancer, including the Rap1 signaling pathway, proteoglycans in cancer, mineral absorption, HTLV-l infection, and central carbon metabolism in cancer. According to the PPI network and the GSE84044 database, seven hub genes associated with liver fibrosis were identified. In addition, qRT-PCR revealed that lncRNA AC100861 (lncRNA TNFRSF10A-DT) was explicitly decreased in liver fibrosis tissues and activated hepatic stellate cells.
In summary, this study preliminarily found that lncRNA TNFRSF10A-DT may be a biomarker for the diagnosis and outcome of liver fibrosis. We uncovered a novel lncRNA-mediated ceRNA regulatory mechanism in the pathogenesis of liver fibrosis.
肝纤维化是一个全球性的健康问题；然而，其分子机制尚不完全清楚。本研究旨在构建 lncRNA-miRNA-mRNA 网络，鉴定潜在相关的 lncRNA，并探讨肝纤维化的发病机制。
我们使用基因表达综合数据库和生物信息学分析方法，鉴定肝纤维化和正常组织之间差异表达的基因（DEGs）。根据 DElncRNA、miRNA 和 DEmRNA 之间的相互作用构建 ceRNA 网络。然后，通过功能富集分析鉴定这些 DEGs，并建立蛋白质-蛋白质相互作用（PPI）网络。采用实时定量聚合酶链反应（qRT-PCR）验证关键 lncRNA。
ceRNA 网络由三个 lncRNA、五个 miRNA 和 93 个 mRNA 组成。基因本体论功能富集分析显示细胞成分、分子功能和生物过程显著增强。京都基因与基因组百科全书通路分析显示与癌症转录失调相关的通路，包括 Rap1 信号通路、癌症中的蛋白聚糖、矿物质吸收、HTLV-1 感染和癌症中的中心碳代谢。根据 PPI 网络和 GSE84044 数据库，鉴定出与肝纤维化相关的七个关键基因。此外，qRT-PCR 显示 lncRNA AC100861（lncRNA TNFRSF10A-DT）在肝纤维化组织和激活的肝星状细胞中明显下调。
综上所述，本研究初步发现 lncRNA TNFRSF10A-DT 可能是肝纤维化诊断和预后的生物标志物。我们揭示了肝纤维化发病机制中一种新的 lncRNA 介导的 ceRNA 调控机制。
