title: [Progesterone-induced microRNA-1a inhibits the proliferation of endometrial epithelial cells].
abstract: The aim of the present study was to investigate the effects of progesterone (P4)-induced microRNA-1a (miR-1a) on the proliferation of endometrial epithelial cells (EECs) and the underlying mechanism. In vivo, following subcutaneous injection of estradiol (E2) alone (E2 group) or combined injections of E2 and P4 (E2P4 group) in ovariectomized mice, quantitative real-time PCR (qPCR) was used to check the expression of miR-1a-3p in the directly isolated mouse EECs. The agomir or antagomir specific for miR-1a-3p was injected into one side of the uterine horns of ovariectomized mice pretreated with E2 alone or in combination with P4, and the non-specific control agomir or antagomir was injected into their contralateral horns. Flow cytometry was used to analyze the cell cycle of EECs. Immunohistochemistry (IHC) was used to examine the location and expression of cyclin D2, cyclin E1, and cyclin E2 in the uterine tissue sections. In vitro, primary cultured mouse EECs were pretreated with E2 alone (E2 group) or in combination with P4 (E2P4 group). qPCR was used to detect the expression of miR-1a-3p. Exogenous mimic of miR-1a-3p was transfected into E2-pretreated EECs, and EdU incorporation analysis was used to test the proliferation activity of the EECs. The result of in vivo experiment showed that the expression of miR-1a-3p in E2P4 group was significantly higher than that in E2 group (P < 0.05). The miR-1a-3p agomir arrested cell cycle at G1 to S transition in the mice injected subcutaneously with E2 alone (P < 0.05). Conversely, silencing of miR-1a-3p with transfection of miR-1a-3p antagomir promoted the entry of cells into S phase in the mice injected subcutaneously with both E2 and P4 (P < 0.05). The expressions of cyclin E1 and cyclin E2, except for cyclin D2, in uterine sections were also dramatically reduced by miR-1a-3p overexpression in the uterine epithelium (P < 0.05). In vitro, miR-1a-3p was not expressed in the cells of both E2 and E2P4 groups. The mimic of miR-1a-3p decreased EECs proliferation activity (P < 0.05). These results indicate that P4-induced miR-1a can inhibit the expression of cyclin E1 and cyclin E2, consequently suppressing the proliferation of mouse EECs by arresting cells at G1/S phase.
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Pan
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Dong-Zhi
authors.initials: DZ
authors.lastname: Yuan
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Jin-Hu
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. yuelimin@scu.edu.cn.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Yue
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells; D004958:Estradiol; D005260:Female; D051379:Mice; D035683:MicroRNAs; D011374:Progesterone; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D014599:Uterus
chemical_list: D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; D011374:Progesterone; D004958:Estradiol