title: MiR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma.
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.
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cogdell
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Limei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Da
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000235:genetics / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; D018398:Homeodomain Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1