MicroRNA-29b/142-5p contribute to the pathogenesis of biliary atresia by regulating the IFN-γ gene.

Cell Death & Disease
Yifan YangShan Zheng

Abstract

Biliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-γ gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers. Meanwhile, the methylation of the LINE-1, ALU and SAT2 repetitive sequences and the IFN-γ promoter was lower, but the expression of IFN-γ was upregulated. After transfected with DNMTs siRNAs, downregulation of DNMTs exerted a significant hypomethylating effect on the repetitive sequences, which led to upregulation of IFN-γ in Jurkat cells. The direct interactions between miR-29b and DNMT3a/3b, and miR-142-5p and DNMT1 were identified using luciferase reporter assays. By transfecting mimics of miR-29b/142-5p into Jurkat cells, we found overexpression of miR-29b/142-5p markedly suppressed expression of DNMTs. Furthermore, the methylation of repetitive sequences and the IFN-γ promoter region were remarka...Continue Reading

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Citations

Jan 4, 2019·Journal of Translational Medicine·Bodo C Melnik, Gerd Schmitz
Mar 25, 2019·Cellular & Molecular Biology Letters·Jian-Yao WangJun Yao
Dec 27, 2018·Current Opinion in Gastroenterology·Muriel Girard, Ganna Panasyuk
Nov 19, 2019·International Journal of Biological Macromolecules·Jing ZhangGang Zhou
Jul 23, 2021·Genes & Diseases·FengXia GaoAiShun Jin
Nov 10, 2021·Toxicology Mechanisms and Methods·Qian ZhangYanli Luo

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Methods Mentioned

BETA
PCR
transfecting
transfection
reverse transcription PCR
electrophoresis
Assay

Software Mentioned

gplots
R
SPSS

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