Long non‑coding RNA MBI‑52 inhibits the development of liver fibrosis by regulating the microRNA‑466g/SMAD4 signaling pathway.

Abstract

Liver fibrosis is a wound healing response triggered by liver injury. In severe cases, it may develop into liver cirrhosis, liver cancer and liver failure. Long non-coding RNAs (lncRNAs) play key roles in the development of liver fibrosis. The present study aimed to investigate the role of lncRNA-MBI-52 (lnc-MBI-52) in the progression of liver fibrosis. Carbon tetrachloride (CCl4)-induced injury was performed to establish a mouse liver fibrosis model, and exogenous transforming growth factor-β1 was used to establish a hepatic stellate cell (HSC) activation model. Reverse transcription-quantitative PCR and western blot analyses were performed to detect mRNA and protein expression, respectively. RNA pull-down assay was performed to assess the interaction between microRNA (miR)-466g and lnc-MBI-52 or SMAD4. Dual-luciferase reporter assay was performed to verify the target of miR-466g. lnc-MBI-52 was overexpressed in CCl4-induced mouse liver fibrosis models and activated HSCs. lnc-MBI-52 knockdown suppressed liver fibrosis in vitro. Moreover, knockdown of lnc-MBI-52 downregulated α-smooth muscle actin and collagen type I expression. In addition, lnc-MBI-52 and SMAD4 were identified as targets of miR-466g. The effects of lnc-MBI-52 on HSC activation were reversed following transfection with miR-466g mimics or SMAD4 knockdown. lnc-MBI-52 miR-466g significantly decreased lnc-MBI-52 expression, while overexpression of lnc-MBI-52 suppressed miR-466g expression. The results of the RNA pull-down assay confirmed the interaction between miR-466g and lnc-MBI-52. Taken together, lnc-MBI-52 induced liver fibrosis by regulating the miR-466g/SMAD4 axis, which may provide a new possible strategy for liver fibrosis.