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Inhibiting the expression of lncRNA-SNHG7 in the liver fibrosis model of mice can alleviate liver fibrosis.
LncRNA-SNHG7 as ceRNA, can bind with miR-29b and affect miR-29b-mediated DNMT3A silencing.
LncRNA-SNHG7 can affect the activation, autophagy and proliferation of hepatic stellate cells via miR-29B/DNMT3A pathway.
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.
Liver fibrosis model of mice was established, primary hepatic stellate cells (HSCs) were cultured from normal mice and induced to activate by TGF-β. 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.
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-β-stimulated normal HSCs, knockdown of SNHG7 expression after shSNHG7 transfection could restrain DNMT3A and HSCs activation factors α-SMA, Collα1 and autophagy-related factors LC3I/II, Beclin1. However, this shSNHG7 effect was reversed by the inhibition of miR-29b.
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.Le texte complet de cet article est disponible en PDF.
Keywords : Liver fibrosis, Hepatic stellate cell, lncRNA-SNHG7, miR-29b, DNMT3A