title: Endometrial miR-200c is altered during transformation into cancerous states and targets the expression of ZEBs, VEGFA, FLT1, IKKβ, KLF9, and FBLN5.
abstract: A number of microRNAs (miRNAs), including miR-200 family, are aberrantly expressed in endometriosis and endometrial cancer. Here we assessed the expression and functional aspects of miR-200c in endometrial tissues (N = 52) from normal endometrial biopsies (N = 15), endometrial tissues including those exposed to hormonal therapies (N = 20), and grade I-III endometrial cancer (N = 17). miR-200c expression was elevated in normal endometrial biopsies from mid- and late-luteal phase, and in endometrial tumors as compared to endometrial tissues from peri- and postmenopausal period (P < .05) and its pattern of temporal expression displayed an inverse relationship with the expression of ZEBs. The expression of E-cadherin (CDH1) varied, but expressed at low levels, specifically in endometrial tissues and endometrial tumors. The endometrial expression of ZEBs and CDH1 in patients who were exposed to Depo-Provera and gonadotropin-releasing hormone agonist GnRHa displayed a trend toward lower expression as compared to proliferative phase; however, treatment of Ishikawa cells with 17β-estradiol, progesterone, and medroxy progesterone acetate had modest effects on the expression of miR-200c and ZEBs without affecting CDH1 expression. Gain of function of miR-200c in Ishikawa cells repressed ZEBs, as well as VEGFA, FLT1, IKKβ, and KLF9 expression at transcriptional and translational levels through direct interaction with their respective 3'untranslated regions and increased the rate of their proliferation. These results indicated that endometrial miR-200c expression undergoes dynamic changes during transition from normal into cancerous states; possibly influenced by hormonal milieu and by targeting the expression of specific genes with key regulatory functions in cellular transformation, inflammation, and angiogenesis may influence these events during normal and disease progression.
authors.affiliation: Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Harekrushna
authors.initials: H
authors.lastname: Panda
authors.forename: Leslie
authors.initials: L
authors.lastname: Pelakh
authors.forename: Tsai-Der
authors.initials: TD
authors.lastname: Chuang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
authors.forename: Orhan
authors.initials: O
authors.lastname: Bukulmez
authors.forename: Nasser
authors.initials: N
authors.lastname: Chegini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D018398:Homeodomain Proteins; C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; D011374:Progesterone; D004958:Estradiol; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D051550:I-kappa B Kinase; C496560:IKBKB protein, human