Abstract
MicroRNAs (miRNAs) have been demonstrated to involve in liver fibrogenesis. However, the miRNA-gene regulation in liver fibrosis is still unclear. Herein, the miRNA expression profile GSE40744 was obtained to analyze the dysregulated miRNAs between liver fibrosis and normal samples. Then, we predicted the target genes of screened miRNAs by miRTarBase, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, the protein-protein interaction (PPI) network was constructed to identify the functional miRNA-gene regulatory modules. Furthermore, we verified the hub gene expression using the gene expression profile GSE14323. Finally, 89 DEMs were identified in fibrotic liver samples compared to normal liver samples. The top 3 upregulated DEMs (miR-200b-3p, miR-200a-3p, and miR-182-5p) and downregulated DEMs (miR-20a-5p, miR-194-3p, and miR-148a-3p) were further studied. 516 and 1416 target genes were predicted, respectively. KEGG analysis demonstrated that the predicted genes were enriched in the p53 signaling pathway and hepatitis B, etc. Through constructing a PPI network, the genes with the highest connectivity were identified as hub genes. Of note, most of the hub genes were potentially targeted by miR-20a-5p and miR-200a-3p. Based on the data from GSE14323, the expression of EGFR, STAT3, CTNNB1, and TP53 targeted by miR-200a-3p was significantly downregulated in fibrotic liver samples. Oppositely, the expression of PTEN, MYC, MAPK1, UBC, and CCND1 potentially targeted by miR-20a-5p was significantly upregulated. In conclusion, it is demonstrated that miR-20a-5p and miR-200a-3p were identified as the novel liver fibrosis-associated miRNAs, which may play critical roles in liver fibrogenesis.
Highlights
Liver fibrosis results from chronic liver disease, which has the potential to progress into cirrhosis, complicating with the loss of architecture and attendant functional failure [1]
It is extensively reported that miRNAs participate in the whole process of liver fibrogenesis, including cell death, the proinflammatory factor secretion by macrophage, and hepatic stellate cell (HSC) activation [11, 30], the profiles of liver fibrosis available are limited
The miR-34a/SIRT1/p53 signaling pathway is activated in liver cells and is a therapeutic target for liver fibrosis
Summary
Liver fibrosis results from chronic liver disease, which has the potential to progress into cirrhosis, complicating with the loss of architecture and attendant functional failure [1]. Compelling evidence indicates that dysregulated expression of miRNAs is found in many types of diseases, including liver fibrosis [7,8,9,10,11]. It is well-studied that many miRNAs are aberrantly expressed in liver tissues from the patients with liver fibrosis. As we know, it is a complicated pathological process of liver fibrogenesis, involving large numbers of miRNAs and genes. MiRNA-221 and miRNA-222 are screened out as the GSE40744/GPL14613, selected samples
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