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 CCl4 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 CCl4-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-1 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.
[1]Fudan Univ, Huashan Hosp, Dept Digest Dis, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China;
[2]Fudan Univ, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China;
[3]Fudan Univ, Sch Life Sci, Dept Anthropol & Human Genet, Minist Educ,Key Lab Contemporary Anthropol, Shanghai 200438, Peoples R China
(8.0+极速模式)