title: Loss of Git2 induces epithelial-mesenchymal transition by miR146a-Cnot6L-controlled expression of Zeb1.
abstract: Epithelial-mesenchymal transition (EMT) can be induced by several pleiotropically activated transcription factors, including the zinc-finger E-box-binding protein Zeb1. Mechanisms regulating Zeb1 expression have been partly uncovered, showing a critical role for the miR-200 family members. In the present study, we show that Zeb1 is regulated by the Arf GTPase-activating protein (GAP) Git2. Following the loss of Git2, we found that miR-146a maturation is enhanced, which in turn promotes the expression of Zeb1 and induction of EMT. Furthermore, we found that Cnot6L, a validated target of miR-146a, affects the stability of Zeb1 mRNA through its deadenylase activity. Our results present evidence for a new role for loss of Git2 in promoting EMT through a novel regulatory pathway.
authors.affiliation: Institute of Molecular and Cell Biology, A STAR, Singapore 138673.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhou
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
mesh_terms: D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012260:Ribonucleases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C430213:GIT2 protein, human; D020690:GTPase-Activating Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C521732:CNOT6L protein, human; D012260:Ribonucleases
keywords: EMT; Git2; Zeb1; miR-146a