Construction of proliferation-related lncRNA-mRNA regulatory network and lncRNA-miRNA-mRNA ceRNA network by bioinformatics analysis

Abstract

Lately, researches on lncRNA-mRNA regulatory network and lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network have been the hotspots, the present study explored the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferation ability of glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) were detected with CCK-8 assay and RNA-seq was performed to study differentially expressed lncRNAs in LPS-induced GMCs. According to the sequencing results, 6 lncRNAs were selected for RT-qPCR validation. Furthermore, lncRNA-mRNA regulatory network and lncRNA-miRNA-mRNA ceRNA network were constructed to examine the role and mechanism of proliferation-related lncRNAs. To reveal the biological functions of lncRNAs, GO biological process and KEGG pathway analysis were we performed on all mRNAs involed in lncRNA-mRNA regulatory network and ceRNA network. Finally, 1532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs were screened out by RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq result. The lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs and lncRNA-miRNA-mRNA ceRNA network, including 6 lncRNAs, 18 miRNAs, and 419 mRNAs were successfully constructed. The GO biological process and KEGG pathway analysis demonstrated that those lncRNAs were mainly related to inflammatory response and substance metabolism. This study first identified key proliferation-related lncRNAs in LPS-induced GMCs, and further revealed a global view of lncRNA-mRNA regulatory network and lncRNA-miRNA-mRNA ceRNA network involved in CGN. Our findings offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and provided promising diagnostic biomarkers.