miR-372-3p Anti-fibroblast Activation by Targeting FBXO11 in Transforming Growth Factor-β1-Induced Human Cardiac Fibroblasts
Objective To investigate the mechanism of FBXO11 expression regulated by microRNA(miRNA)and its molecular mechanism in the activating process of cardiac fibroblasts.Methods Human normal cardiac fibroblasts(hCFs)were transfected with miR-372-3p mimics and induced by transforming growth factor-β1(TGF-β1),and qRT-PCR was used to detect FBXO11 as well as the expression of hCFs activation markers;the binding of FBXO11 to MiR-372-3p was detected by dual luciferase reporter gene assay.Results Upon hCFs activation,the expression of FBXO11 was upregulated in dose-dependent manner and positively correlated with the activation markers of hCFs.After the knockdown of FBXO11,the expression of activation markers of hCFs was downregulated.In vitro,in a TGF-β1-induced fibrosis model of hCFs,MiR-372-3p expression was down-regulated and significantly negatively correlated with FBXO11.MiR-372-3p was up-regulated in an in TGF-β1-induced fibrosis model of hCFs by binding to the FBXO11 3'untranslated region(3'UTR).Overexpression of miR-372-3p inhibited TGF-β1-induced high FBXO11 expression and elevated levels of hCFs activation markers.Conclusion miR-372-3p is involved in the anti-hCFs activation by negatively regulating FBXO11 expression.