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Suppressing microRNA-29c promotes biliary atresia-related fibrosis by targeting DNMT3A and DNMT3B
- 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.
- Subjects :
- 0301 basic medicine
Epithelial-Mesenchymal Transition
Short Report
Vimentin
MiR-29c
Biochemistry
DNA Methyltransferase 3A
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Fibrosis
medicine
Humans
DNA (Cytosine-5-)-Methyltransferases
Epithelial–mesenchymal transition
lcsh:QH573-671
Molecular Biology
biology
lcsh:Cytology
Chemistry
Infant
Cell Biology
Transfection
medicine.disease
Molecular medicine
Blot
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Lipofectamine
030220 oncology & carcinogenesis
embryonic structures
Cancer research
biology.protein
DNMT3A
DNMT3B
Biliary atresia
Subjects
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