title: MicroRNA-106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines.
abstract: Type II endometrial carcinoma is an aggressive subtype of endometrial cancer (EC). TWIST1, a helix-loop-helix transcription regulator, is known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) also serve as important regulators of EMT and metastasis by regulating EMT-related genes. In this study, we sought to explore the role of TWIST1 in inducing EMT in representative type II EC cell lines, and to determine the miRNAs involved in regulating TWIST1 gene expression. Functional analysis suggested that TWIST1 contributes to the EMT phenotypes of EC cells, as evidenced by the acquisition of fibroblast-like properties, enhanced invasiveness, and induction of an EN-switch (downregulation of epithelial marker E-cadherin and upregulation of mesenchymal marker N-cadherin). Conversely, silencing of TWIST1 by siRNA inhibited cell invasion and the mesenchymal phenotype, which was accompanied by a reversion of the EN-switch. We also observed a novel post-transcriptional regulatory mechanism of TWIST1 expression mediated by miR-106b via its direct interaction with TWIST1 mRNAs at the 3'-untranslated region. Our data suggest that TWIST1 is a critical inducer of EMT in invasive EC cells and that miR-106b could suppress EC cell invasion by downregulating TWIST1 expression.
authors.affiliation: Department of Women's Health Educational System, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Peixin
authors.initials: P
authors.lastname: Dong
authors.forename: Masanori
authors.initials: M
authors.lastname: Kaneuchi
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Watari
authors.forename: Satoko
authors.initials: S
authors.lastname: Sudo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D008156:Luciferases
keywords: EMT; TWIST1; endometrial cancer; miRNA