title: MicroRNA-302b suppresses human epithelial ovarian cancer cell growth by targeting RUNX1.
abstract: BACKGROUND
  The microRNA (miR)-302 family functions as a tumor suppressor in human cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. Here, we investigated the role of miR-302b and its target gene RUNX1 in EOC.
  
  
  METHODS
  The expression levels of miR-302b and RUNX1 were assessed by quantitative real-time PCR and western blotting. The effects of ectopic expression of miR-302b were evaluated by the MTT assay, colony forming assay and flow cytometry. RUNX1 was identified as a target of miR-302b and their interaction was confirmed by luciferase activity assays, RUNX1 silencing and overexpression of a RUNX1 mutant construct lacking the 3'UTR. The effect of miR-302b on the suppression of tumor growth was investigated in vivo in a xenograft mouse model.
  
  
  RESULTS
  MiR-302b levels were markedly decreased in EOC specimens. Ectopic expression of miR-302b in EOC cells inhibited cell proliferation and colony formation, induced G0/G1 arrest, and promoted apoptosis. RUNX1 was identified as a direct target of miR-302b, and knockdown of RUNX1 inhibited cell growth in a manner similar to miR-302b overexpression, whereas introduction of a 3'UTR mutant of RUNX1 reversed the suppressive effect of miR-302b. Furthermore, miR-302b overexpression led to the inactivation of the STAT3 signaling pathway in EOC cells and inhibited tumor growth in a xenograft mouse model.
  
  
  CONCLUSIONS
  MiR-302b functions as a tumor suppressor in EOC by targeting RUNX1 and modulating the activity of the STAT3 signaling pathway.
authors.affiliation: Department of Gynecology, the Affiliated Tumor Hospital, Harbin Medical University, Harbin, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ge
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Yin
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Tianbo
authors.initials: T
authors.lastname: Liu
authors.forename: Ge
authors.initials: G
authors.lastname: Lou
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; C493728:RUNX1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human