title: Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3.
abstract: BACKGROUND
  Evidence suggests that a number of microRNA (miRNA) are aberrantly expressed in endometrial disorders with potential posttranscriptional regulation of their specific target genes, including ovarian steroid receptors.
  
  
  OBJECTIVE
  Our objective was to assess the endometrial expression of miR-98 and miR-181a and their respective target genes, progesterone (P4) receptor membrane component 1 (PGRMC1) and P4 receptor (PGR).
  
  
  METHODS
  We evaluated tissue expression and in vitro regulation at an academic university medical center in endometrial biopsies and endometrial tissues from follicular and luteal phases with and without exposure to hormonal therapies and grade I-III endometrial cancer (n = 52).
  
  
  METHODS
  INTERVENTIONS included endometrial biopsies and in vitro transfection.
  
  
  METHODS
  We evaluated expression and function of miR-98 and miR-181a.
  
  
  RESULTS
  Aberrant expression of miR-98 and miR-181a is associated with endometrial transition from normal into cancerous states, which to some extent is influenced by hormonal milieu, and exhibited an inverse relationship with PGMRC1 and PGR expression, respectively. Treatments of Ishikawa cells with 17β-estradiol, P4, or medroxyprogesterone acetate had limited effects on miR-98, miR-181a, and PGRMC1 expression, whereas 17β-estradiol treatment increased PGR expression. In Ishikawa cells, gain of function of miR-98 repressed PGRMC1 and CYP19A1, and miR-181a repressed PGR, DDX3X, and TIMP3 at mRNA and protein levels through direct interactions with their respective 3'-untranslated regions and CCNE1 through miR-181a-induced DDX3X repression, with miR-98 reducing the rate of cell proliferation as compared with controls.
  
  
  CONCLUSIONS
  miR-98 and miR-181a through their regulatory functions on PGRMC1, PGR, CYP19A1, TIMP3, and DDX3X expression may influence a wide range of endometrial cellular activities during normal menstrual cycle and transition into disease states, including endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Harekrushna
authors.initials: H
authors.lastname: Panda
authors.forename: Tsai-Der
authors.initials: TD
authors.lastname: Chuang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
authors.forename: Nasser
authors.initials: N
authors.lastname: Chegini
mesh_terms: D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C546084:MIRN98 microRNA, human; C540193:MIrn181 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C115296:PGRMC1 protein, human; D011980:Receptors, Progesterone; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D001141:Aromatase; C561410:CYP19A1 protein, human; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases