miR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma

Guo,Fei; Cogdell,David; Hu,Limei; Yang,Da; Sood,Anil K.; Xue,Fengxia; Zhang,Wei

doi:10.3892/or.2014.3106

miR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma

Authors:
- Fei Guo
- David Cogdell
- Limei Hu
- Da Yang
- Anil K. Sood
- Fengxia Xue
- Wei Zhang
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Affiliations: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: March 21, 2014 https://doi.org/10.3892/or.2014.3106
Pages: 2021-2028

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Abstract

Ovarian carcinoma is the most lethal gynecologic malignancy; the majority of patients succumb to the disease within 5 years of diagnosis. The poor survival rate is attributed to diagnosis at advanced stage, when the tumor has metastasized. The epithelial-to-mesenchymal transition (EMT) is a necessary step toward metastatic tumor progression. Through integrated computational analysis, we recently identified a master microRNA (miRNA) network that includes miR-101 and regulates EMT in ovarian carcinoma. In the present study, we characterized the functions of miR-101. Using reporter gene assays, we demonstrated that miR-101 suppressed the expression of the E-cadherin repressors ZEB1 and ZEB2 by directly targeting the 3'-untranslated region (3'UTR) of both ZEB1 and ZEB2. Introduction of miR-101 significantly inhibited EMT and cell migration and invasion. Introducing cDNAs of ZEB1 and ZEB2 without 3'UTR abrogated miR-101-induced EMT alteration, respectively. Our findings showed that miR-101 represents a redundant mechanism for the miR-200 family that regulates EMT through two major E-cadherin transcriptional repressors.

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