Integration of high-throughput data of microRNA and mRNA expression profiles reveals novel insights into the mechanism of liver fibrosis

Numerous studies have revealed that microRNAs (miRNAs) are functional non-coding RNAs that serve roles in a variety of biological processes. However, the expression patterns and regulatory networks, as well as the miRNAs involved in liver fibrosis remain to be elucidated. In the present study, a mouse model of liver fibrosis was constructed by CCl(4) intraperitoneal injection and the total RNAs were extracted from the liver of the mice. The total RNAs were then sequenced on an Illumina HiSeq 2000 platform and an integrated analysis of miRNA and mRNA expression profiles in CCl(4)-induced liver fibrosis was performed. Compared with normal liver samples, 56 and 15 miRNAs were found to be upregulated and downregulated in fibrotic livers, respectively. To predict the potential functions of these miRNAs, bioinformatics analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, was used to assess target mRNAs. The results indicated that the mitogen-activated protein kinase, phosphoinositide 3 kinase/protein kinase B and focal adhesion signaling pathways were the most significantly enriched. In addition, a regulatory network containing five dysregulated miRNAs and 22 target mRNAs was constructed based on their inverse correlation. Furthermore, the five dysregulated miRNAs were significantly upregulated and the expression of RELB, RAP1A, PPP3CB, MAP2K4, ARRB1, MAP3K4, FGF1 and PRKCB in the network was significantly decreased in LX-2 cells following TGF-β1 treatment which suggested that they were associated with the activation of human hepatic stellate cells. The miRNA-mRNA regulatory network produced in the present study may provide novel insights into the role of miRNAs in liver fibrosis.