miR-30 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in hepatocyte by targeting Snail1.
Epithelial-to-mesenchymal transition (EMT) has been implicated in embryonic development and various pathological events. Snail1 is a well-known E-cadherin-transcriptional repressor that is significantly upregulated during the TGF-β1-induced EMT in hepatocyte. However, the functional involvement of microRNA during the EMT process in hepatocyte remains to be determined. Here, we revealed that while the expression of Snail1 increased during the TGF-β1-induced EMT in AML12 murine hepatocytes, the expression of miR-30 family members exhibited significant downregulation. Computational microRNA target predictions detected a conserved sequence matching to the seed region of miR-30 in the 3'UTR of Snail1 mRNA. Our results demonstrated that miR-30 could negatively regulate the expression of Snail1 by direct targeting the predicted binding site. More importantly, transfection of miR-30b mimics significantly inhibited the TGF-β1-induced EMT in AML12 cells as assessed through cell morphology changes and the expression profiles of Snail1, E-cadherin and other fibroblast markers. Finally, we demonstrated that TGF-β1-induced hepatocyte migration was greatly suppressed in cells transfected with miR-30b mimics. Our results provide a new insight into the role of miR-30 in regulating EMT, which could be of importance in understanding the related physiologic and pathologic processes.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, PR China.
Jingcheng
J
Zhang
Haiyan
H
Zhang
Junyu
J
Liu
Xiaolong
X
Tu
Yuhui
Y
Zang
Jie
J
Zhu
Jiangning
J
Chen
Lei
L
Dong
Junfeng
J
Zhang
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D020413:3' Untranslated Regions; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1