RRC ID 72563
Author Dong P, Kaneuchi M, Watari H, Sudo S, Sakuragi N.
Title MicroRNA-106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines.
Journal Mol Carcinog
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.
Volume 53(5)
Pages 349-59
Published 2014-5-1
DOI 10.1002/mc.21983
PMID 24002805
MeSH 3' Untranslated Regions Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / pathology* Apoptosis Blotting, Western Cadherins / genetics Cadherins / metabolism Cell Adhesion Cell Movement* Cell Proliferation Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology* Epithelial-Mesenchymal Transition* Female Gene Expression Regulation, Neoplastic Humans Luciferases / metabolism MicroRNAs / antagonists & inhibitors MicroRNAs / genetics* Neoplasm Invasiveness Nuclear Proteins / antagonists & inhibitors Nuclear Proteins / genetics Nuclear Proteins / metabolism* RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Twist-Related Protein 1 / antagonists & inhibitors Twist-Related Protein 1 / genetics Twist-Related Protein 1 / metabolism*
IF 3.825
Human and Animal Cells HOUA-I(RCB0659)