Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in hepatic fibrosis

Hepatic fibrosis (HF), one of the leading global health problems, is defined as aberrant and excess production of extracellular matrix components. The pathogenesis of HF is complex and poorly understood. Long non-coding RNAs (LncRNAs) can interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate the expression of target genes, which play a significant role in the initiation and progression of HF. In the present study, the LncRNA-associated ceRNA network was reconstructed based on LncRNA, miRNA and mRNA expression profiles that were downloaded from National Center for Biotechnology Information Gene Expression Omnibus. Bioinformatics assessments including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed with Database for Annotation, Visualization and Integration Discovery. The ceRNA network was composed of 220 LncRNA nodes, 24 miRNA nodes, 164 mRNA nodes and 1,149 edges. Functional assays identified that a total of 338 GO terms and 25 pathways, including regulation of cytokine and collagen, and the transforming growth factor-beta and Toll-like receptor signaling pathways, were significantly enriched. In addition, 4 LncRNAs (NONMMUT036242, XR_877072, XR_378619 and XR_378418) were highly related to HF and thereby chosen as key LncRNAs. The present study uncovered a ceRNA network that could further the understanding of the mechanisms underlying HF development and provide potential novel markers for clinical diagnosis and targets for treatment.