Liver fibrosis is a common pathological feature of
end-stage liver disease and has no effective treatment.
MicroRNAs (
miRNAs) have been found to modulate gene expression in
liver disease. But the potential role of
miRNA in hepatic
fibrosis is still unclear. The objective of this research is to study the potential mechanism and biological function of miR-183-5p in
liver fibrosis. In this study, we used high-throughput sequencing to find that miR-183-5p is upregulated in human fibrotic liver tissues. In addition, miR-183-5p was upregulated both in rat
liver fibrosis tissue induced by bile-duct
ligation (BDL) and activated LX-2 cells (human hepatic stellate cell line) according to the result of quantitative real-time PCR (RT-qPCR). Moreover, the inhibition of miR-183-5p alleviated
liver fibrosis, decreased the fibrotic
biomarker levels in vitro and in vivo, and led toLX-2 cell proliferation inhibition and, apoptosis induction. The result of dual-
luciferase assay revealed that miR-183-5p suppressed fork head box
protein O1 (FOXO1) expression by binding to its
3'UTR directly. Next, we used lentivirus to overexpress FOXO1 in LX-2 cells, and we found that overexpression of FOXO1 reversed the promotion of miR-183-5p on
liver fibrosis, reducing the fibrotic
biomarker levels inLX-2 cells, inhibitingLX-2 cell proliferation, and promoting apoptosis. Furthermore, overexpression of FOXO1 prevented the activation of the
transforming growth factor (TGF)-β signaling pathway in TGF-β1-induced LX-2 cells according to the result of western blotting. In conclusion, the findings showed thatmiR-183-5p might act as a key regulator of
liver fibrosis, and miR-183-5p could promote cholestatic
liver fibrosis by inhibiting FOXO1 expression through the TGF-β signaling pathway. Thus, inhibition of miR-183-5pmay be a new way to prevent and improve
liver fibrosis.