title: miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression.
abstract: This study was to investigate the effect of miR-200c on regulation of ovarian cancer cell metastasis potential and explore the underlying molecular events. qRT-PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and 30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c expression in ovarian cancer cells for detection of changed phenotypes of tumor cells. Bioinformatics analysis was then used to predict target genes of miR-200c and GO and pathway analyses drew the miR-200c-related gene network. Luciferase reporter assay confirmed the target of miR-200c as ZEB2. Western blot was used to detect gene expressions in ovarian cancer cells. Level of miR-200c expression was much higher in ovarian cancer than in normal ovarian tissues, and miR-200c expression was inversely associated with advanced clinical stage and lymph node metastasis of ovarian cancer (p < 0.01). The database search predicted 186 miR-200c-targeting genes, and GO analysis showed that functions of these target genes were enriched in the protein binding and other biological processes. Furthermore, miR-200c expression inhibited ovarian cancer cell ES-2 migration and invasion capacity by suppression of ZEB2 expression (p < 0.01). Overexpression of miR-200c regulated E-cadherin and vimentin expression in ovarian cancer cells. This study demonstrated high miR-200c expression in ovarian cancer tissues and ZEB2 as a targeting gene of miR-200c, which mediated the effects of miR-200c on regulation of ovarian cancer cell migration and invasion capacity and epithelial-to-mesenchymal transition. Thus, targeting of miR-200c or ZEB2 may serve as a potential therapeutic strategy for control of ovarian cancer.
authors: Department of Gynecology and Obstetrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang, 110003, China.
authors: Yan-ming
authors: YM
authors: Lu
authors: Chao
authors: C
authors: Shang
authors: Yang-ling
authors: YL
authors: Ou
authors: Duo
authors: D
authors: Yin
authors: Yi-ning
authors: YN
authors: Li
authors: Xiang
authors: X
authors: Li
authors: Ning
authors: N
authors: Wang
authors: Shu-lan
authors: SL
authors: Zhang
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012016:Reference Values; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014746:Vimentin; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2