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

Authors :
Hao Cheng
Yongqin Ye
Qi Feng
Yue-lan Zheng
Jian-yao Wang
Jun Yao
Bin Wang
Zimin Chen
Zhouguang Wu
Hong-yan Zhang
Source :
Cellular & Molecular Biology Letters, Vol 24, Iss 1, Pp 1-11 (2019), Cellular & Molecular Biology Letters
Publication Year :
2019
Publisher :
Springer Science and Business Media LLC, 2019.

Abstract

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.

Details

ISSN :
16891392 and 14258153
Volume :
24
Database :
OpenAIRE
Journal :
Cellular & Molecular Biology Letters
Accession number :
edsair.doi.dedup.....16e6628e16998558c3002fd0aade2ff6
Full Text :
https://doi.org/10.1186/s11658-018-0134-9