title: Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells.
abstract: This study aimed to understand the role of miR-133a in progesterone actions, explore the regulative mechanism of the progesterone receptor, and investigate the effects of miR-133a on the progesterone-inhibited proliferation of mouse endometrial epithelial cells.
  
  
  
  The expression of miR-133a induced by progesterone was detected by quantitative real-time PCR both in vivo and in vitro. Ishikawa subcell lines stably transfected with progesterone receptor subtypes were used to determine the receptor mechanism of progesterone inducing miR-133a. Specific miR-133a mimics or inhibitors were transfected into mouse uteri and primary cultured endometrial epithelial cells to overexpress or downregulate the miR-133a. The roles of miR-133a in the cell cycle and proliferation of endometrial epithelial cells were analysed by flow cytometry and Edu incorporation analysis. The protein levels of cyclinD2 in uterine tissue sections and primary cultured endometrial epithelial cells were determined by immunohistochemistry and Western blot analysis.
  
  
  
  Progesterone could induce miR-133a expression in a PRB-dependent manner in endometrial epithelial cells. miR-133a inhibited endometrial epithelial cell proliferation by arresting cell cycle at the G1-S transition. Moreover, miR-133a acted as an inhibitor in downregulating cyclinD2 in endometrial epithelial cells.
  
  
  
  We showed for the first time that progesterone-induced miR-133a inhibited the proliferation of endometrial epithelial cells by downregulating cyclinD2. Our research indicated an important mechanism for progesterone inhibiting the proliferation of endometrial epithelial cells by inducing special miRNAs to inhibit positive regulatory proteins in the cell cycle.
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: J-L
authors.initials: JL
authors.lastname: Pan
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: D-Z
authors.initials: DZ
authors.lastname: Yuan
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Y-B
authors.initials: YB
authors.lastname: Zhao
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: L
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: J-H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Blok
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: C W
authors.initials: CW
authors.lastname: Burger
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: L-M
authors.initials: LM
authors.lastname: Yue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D056742:Cyclin D2 / Q000096:biosynthesis*; D004717:Endometrium / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D056742:Cyclin D2; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D011374:Progesterone
keywords: cyclinD2; endometrium epithelium; miR-133a; progesterone