Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and endometrial carcinoma

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Oliver Zierau - , Umweltmonitoring und Endokrinologie (FoG) (Autor:in)
  • Janina Helle - (Autor:in)
  • Sabina Schadyew - (Autor:in)
  • Yanni Morgenroth - (Autor:in)
  • Martin Bentler - (Autor:in)
  • Alexander Hennig - (Autor:in)
  • Sridar Chittur - (Autor:in)
  • Martin Tenniswood - (Autor:in)
  • Georg Kretzschmar - (Autor:in)

Abstract

The role of microRNAs (miRNA) in estrogen receptor (ER) signaling in the uterus and in endometrial cancer is not well understood. We therefore analyzed miRNA expression in uterine samples from a standard 3-day uterotrophic assay using young female adult rats to identify E2-regulated miRNAs. Microarray analysis identified 47 E2 down-regulated miRNAs including miR-30a, and 25 E2up-regulated miRNAs including miR-672, miR-203, and miR-146b. The strongly E2-upregulated miR-203 was selected for further analysis. miR-203 was deleted in the rat endometrial adenocarcinoma cell line, RUCA-I, using CRISPR/CAS9. Five clones devoid of miR-203 expression were generated. Proliferation was reduced and G2-arrest was observed in all miR-203 deficient RUCA-I clones. Transfection with a miR-203-3p mimic partially rescues this effect. Comparison of mRNA expression in three miR-203 knockout clones to wild type RUCA-I cells reveals 566 miR-203-upregulated and 592 miR-203-downregulated genes. 43 of the genes that are upregulated by miR-203 knockout in vitro are downregulated in the uterus by E2. Of these Acer2, Zbtb20, Ptn, Rcbtb2, Mum1l1, Hmgn3, and Nfat5 possess one or more seed sequence matches in their 3'-UTR that are predicted to be targets of miR-203. These data demonstrate the importance of E2 regulated miRNAs in general, and miR-203 in particular, for E2 regulated gene expression and physiological processes including proliferation and cell migration, in the uterus as well as in the etiology of endometrial carcinomas.

Details

OriginalspracheEnglisch
Seiten (von - bis)5359-5372
Seitenumfang14
FachzeitschriftJournal of cellular biochemistry
Jahrgang119
Ausgabenummer7
PublikationsstatusVeröffentlicht - 13 Jan. 2018
Peer-Review-StatusJa

Externe IDs

Scopus 85043720683

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Animals, Base Sequence, Cell Cycle, Cell Proliferation, Endometrial Neoplasms/drug therapy, Estrogens/pharmacology, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic/drug effects, MicroRNAs/genetics, Rats, Rats, Inbred Lew, Receptors, Estrogen/genetics, Sequence Homology, Signal Transduction/drug effects, Uterus/drug effects