title: MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-α.
abstract: BACKGROUND
  Endometrial carcinoma (EC) is one of the most lethal gynecologic cancers. Patients frequently have regional or distant metastasis at diagnosis. MicroRNAs are small non-coding RNAs that participate in numerous biological processes. Recent studies have demonstrated that miR-505 is associated with several types of cancer; however, the expression and function of miR-505 have not been investigated in EC.
  
  
  METHODS
  miR-505 expression in normal endometrial tissue, endometrial carcinomas were quantified by Quantitative reverse transcription PCR. The endometrial carcinoma cell lines HEC-1B and Ishikawa were each transfected with miR-505 or scrambled mimics, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-505 and its target gene TGF-α.
  
  
  RESULTS
  RT-PCR results demonstrated that miR-505 was significantly downregulated in human EC tissues compared to normal endometrial tissues. Besides, miR-505 expression was negatively associated with FIGO stage (stage I-II vs. III-IV), and lymph node metastasis (negative vs. positive). In vitro, overexpression of miR-505 significantly suppressed EC cell proliferation, increased apoptosis and reduced migratory and invasive activity. A miR-505 binding site was identified in the 3' untranslated region of TGF-α mRNA (TGFA) using miRNA target-detecting software; a dual luciferase reporter assay confirmed that miR-505 directly targets and regulates TGFA. RT-PCR and Western-blotting results indicated that overexpressing miR-505 reduced the expression of TGF-α and the TGF-α-regulated proteins MMP2, MMP9, CDK2, while induced Bax and cleaved-PARP expression in EC cells. In vivo, overexpression of miR-505 reduced the tumorigenicity and inhibited the growth of xenograft tumors in a mouse model of EC.
  
  
  CONCLUSIONS
  Taken together, this study demonstrates that miR-505 acts as tumor suppressor in EC by regulating TGF-α.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Sun
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 100013, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. yida.zhaoyang@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C574053:MIRN505 microRNA, human; D035683:MicroRNAs; D016211:Transforming Growth Factor alpha
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