title: Effect of miR-29c and miR-129-5p on epithelial-mesenchymal transition in experimental biliary atresia mouse models.
abstract: Biliary atresia (BA) is a destructive bile duct disease occurring in newborn children within a few weeks after birth. In this study, the effect of miR-29c and miR-129-5p on epithelial-mesenchymal transition (EMT) in experimental BA was explored by constructing BA mouse models via Rhesus rotavirus vaccine infection. miR-29c and miR-129-5p expression was analyzed by real-time quantitative polymerase chain reaction. EMT was established by induction with transforming growth factor (TGF)-β1. miR-29c and miR-129-5p were overexpressed and inhibited, respectively, by Lipofectamine transfection. EMT-related protein (formin-like 2, FMNL2; E-cadherin; vimentin; and cytokeratin-19, CK-19) expression was analyzed by western blot and immunofluorescent assay. The results indicated that miR-29c and miR-129-5p were downregulated and upregulated in BA mice. TGF-β1 induction caused a time-dependent decrease and increase in miR-29c and miR-129-5p, respectively. Additionally, TGF-β1 induced an increase in FMNL2 and vimentin expression and a decrease in E-cadherin and CK-19 expression (P < 0.05). Overexpression or suppression of miRNA-29c or miR-129-5p, respectively, induced the inhibition of FMNL2 and vimentin, and promotion of E-cadherin and CK-19 expression, in the test groups compared to the non-intervention group (P < 0.05). However, the FMNL2, vimentin, E-cadherin, and CK- 19 expression did not differ between the control and non-intervention groups (P > 0.05). Thus, miR-29c upregulation or miR-129-5p downregulation effectively prevented EMT in BA by regulating the expression of EMT pathway-related proteins. Therefore, miR-29c and miR-129-5p could be utilized as therapeutic targets for BA in the future.
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: M
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: X S
authors.initials: XS
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China liulei0718@yeah.net.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People's Hospital, Shenzhen, Guangdong Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Yao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001656:Biliary Atresia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D000080865:Formins; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C000611838:Cdh1 protein, mouse; C000592815:FMNL2 protein, mouse; D000080865:Formins; D047908:Intracellular Signaling Peptides and Proteins; D053539:Keratin-19; C000614367:MIRN129 microRNA, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D022243:Rotavirus Vaccines; D053773:Transforming Growth Factor beta1; D014746:Vimentin