Suppressing microRNA-29c promotes biliary atresia-related fibrosis by targeting DNMT3A and DNMT3B

Cellular & Molecular Biology Letters

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[1] 0000 0000 9678 1884, grid.412449.e, Graduate School of China Medical University, 110122, Shenzhen, Liaoning Province, China;0000 0004 1790 3548, grid.258164.c, Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, 518020, Shenzhen, Guangdong Province, China;0000 0004 1806 5224, grid.452787.b, Department of General Surgery, Shenzhen Children’s Hospital, 518026, Shenzhen, Guangdong Province, China;

关键词: Biliary atresia;    Epithelial–mesenchymal transition;    MiR-29c;    Fibrosis;    DNMT3A;    DNMT3B;   

DOI  :  10.1186/s11658-018-0134-9

来源: publisher

【 摘 要 】

This study was designed to investigate the potential role of microRNA-29c (miR-29c) in biliary atresia-related fibrosis. The expression of miR-29c was determined in 15 pairs of peripheral blood samples from infants with biliary atresia (BA) and infants with non-BA neonatal cholestasis using quantitative real-time PCR. EMT was established by induction with TGF-β1 in HIBEpiC cells. MiR-29c was inhibited by lipofectamine transfection. The expressions of proteins related to epithelial–mesenchymal transition (EMT), i.e., E-cadherin, N-cadherin and vimentin, were determined using quantitative real-time PCR and western blotting. Direct interaction between miR-29c and DNMT3A and DNMT3B was identified using a luciferase reporter assay. The expressions of DNMT3A and DNMT3B were suppressed by treatment with SGI-1027. Patients with BA showed significantly lower miR-29c levels in peripheral blood samples than the control subjects. In vitro, TGF-β1-induced EMT significantly decreased the expression of miR-29c. Downregulation of miR-29c had a promotional effect on BA-related fibrosis in HIBEpiC cells, as confirmed by the decrease in E-cadherin and increase in N-cadherin and vimentin levels. MiR-29c was found to target the 3’UTR of DNMT3A and DNMT3B and inhibit their expression. Suppression of DNMT3A and DNMT3B reversed the effects of miR-29c downregulation on BA-related fibrosis in HIBEpiC cells. These data suggest that BA-related fibrosis is closely associated with the occurrence of EMT in HIBEpiC cells. MiR-29c might be a candidate for alleviating BA-related fibrosis by targeting DNMT3A and DNMT3B.

【 授权许可】

CC BY