LncRNA-SNHG7/miR-29b/DNMT3A axis affects activation, autophagy and proliferation of hepatic stellate cells in liver fibrosis

Objectives: To determine the relative expression of long non-coding small nucleolar RNA host gene 7 (lncRNA-SNHG7) in fibrotic liver and hepatic stellate cells, and investigate the biological effects and mechanisms of SNHG7 on liver fibrosis. Methods: Liver fibrosis model of mice was established, primary hepatic stellate cells (HSCs) were cultured from normal mice and induced to activate by TGF-beta. Cell viability, proliferation, and autophagy were detected with MTT, BrdU, and MDC stain, respectively. Liver tissue stained with Masson and Sirius Red. The interaction between SNHG7 and miR-29b was investigated by immunoprecipitation, RNA pull-down and Dual-luciferase reporter gene assay. The effects of SNHG7 on the expression of miR-29b, DNMT3A and liver fibrosis related factors were detected in vitro or in vivo transfection experiments. Results: SNHG7 was signally increased in liver tissue and HSCs of liver fibrosis model of mice, and inhibition of SNHG7 expression in liver fibrosis mice can reduce liver fibrosis. We also found that SNHG7 could bind to miR-29b in HSCs and inhibit the expression of miR-29b. In TGF-beta-stimulated normal HSCs, knockdown of SNHG7 expression after shSNHG7 transfection could restrain DNMT3A and HSCs activation factors et-SMA, Collo1 and autophagy-related factors LC3I/II, Beclin1. However, this shSNHG7 effect was reversed by the inhibition of miR-29b. Conclusion: Inhibition of lncRNA-SNHG7 can inhibit liver fibrosis. This is partly due to SNHG7 acts as a competitive endogenous RNA (ceRNA) to affect the expression of DNMT3A, a downstream target gene of miR-29b, by binding to miR-29b, thereby affecting the activation, autophagy and proliferation of HSCs. (C) 2020 Published by Elsevier Masson SAS.

Automated summary

Inhibition of lncRNA-SNHG7 can attenuate liver fibrosis by acting as a ceRNA to modulate the expression of DNMT3A through miR-29b, thereby affecting the activation, autophagy, and proliferation of HSCs.