MicroRNA-506-3p Regulated the Proliferation of Hepatic Stellate Cells during Liver Fibrosis

摘要

Long-term chronic liver disease may result in hepatic fibrosis, which lacks effective treatment at present. MiRNA-506-3p (miR-506) has been widely reported as an essential regulator in various pathological processes, especially carcinogenesis. However, it is still unknown whether and how it acts in the liver fibrosis (LF). Here we revealed the molecular mechanism of miR-506 in regulation of hepatic stellate cell (HSC) viability, apoptosis, and cytokine production. Reduced miR-506 expression was first confirmed in 10 hepatic specimens of LF patients and HSC cell line LX-2, compared to that from healthy hepatic tissue and normal hepatic cell. Conversely, augment of P65 was observed in hepatic specimens and LX-2 cells. Dual-luciferase reporter assay identified that miR-506 targets the 3'-UTR of the P65 gene for silencing. MTT, BrdU incorporation, and colony formation assays showed that miR-506 attenuated cell viability of LX-2 cells. Hoechst 33342 staining and Annexin V-FITC/PI analysis displayed that overexpression of miR-506 promoted apoptotic level of LX-2 cells, which is further verified by decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax expression. Together, our study provided evidences for probing the molecular mechanisms of LF pathogenesis and new therapeutic approaches for its treatment.