title: Up-regulation of microRNA-145 promotes differentiation by repressing OCT4 in human endometrial adenocarcinoma cells.
abstract: BACKGROUND
  MicroRNA-145 (miR-145) has been reported to be a tumor-suppressing agent in several studies. It can repress pluripotency and control human embryonic stem cell differentiation by regulating the core pluripotency factor OCT4. However, it is not known whether miR-145 can play a role in inducing tumor cell differentiation and repressing growth of tumors.
  
  
  METHODS
  Ishikawa cells, the established human endometrial cancer cells, were treated with miR-145 mimics, inhibitor, or small interfering RNA OCT4. miR-145 levels were assayed using TaqMan microRNA assays, and the messenger RNA levels of OCT4 and the differentiation marker glycodelin were measured using real-time polymerase chain reaction. The protein levels of OCT4 and glycodelin were characterized via flow cytometry, western blotting, and immunohistochemistry. In vivo activity was measured in a xenograft mouse model.
  
  
  RESULTS
  Up-regulating miR-145 reduced the expression of OCT4 and induced the differentiation of Ishikawa cells to closely resemble normal endometrial epithelium both in vitro and in vivo. miR-145 successfully inhibited tumor growth. We also found that in patients with endometrial carcinoma, miR-145 and OCT4 were expressed in tissues, and there was a relationship between miR-145, OCT4, and the degree of tumor cell differentiation.
  
  
  CONCLUSIONS
  Our results strongly suggested that miR-145 is a tumor cell differentiation-inducing agent in endometrial carcinoma, and that miR-145 or OCT4 may be useful markers for grading endometrial carcinoma.
authors.affiliation: Department of Obstetrics & Gynecology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Wu
authors.forename: Shupeng
authors.initials: S
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Edward
authors.initials: E
authors.lastname: Younglai
authors.forename: Shuhan
authors.initials: S
authors.lastname: Sun
authors.forename: Huilan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000032:analysis / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human