title: MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer.
abstract: OBJECTIVE
  The process of metastases involves the dissociation of cells from the primary tumor, penetration into the basement membrane, invasion, and exiting from the vasculature to seed and colonize distant tissues. miR-200a is involved in this multistep metastatic cascade. This study aimed to test the hypothesis that miR-200a promotes metastasis through increased anoikis resistance in breast cancer.
  
  
  METHODS
  Breast cancer cells transfected with mimic or inhibitor for miR-200a were assayed for anoikis in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR). Luciferase assays, colony formation assays, and animal studies were conducted to identify the targets of miR-200a and the mechanism by which it promotes anoikis resistance.
  
  
  RESULTS
  We found that overexpression of miR-200a promotes whereas inhibition of miR-200a suppresses anoikis resistance in breast cancer cells. We identified Yes-associated protein 1 (YAP1) as a novel target of miR-200a. Our data showed that targeting of YAP1 by miR-200a resulted in decreased expression of proapoptotic proteins, which leads to anoikis resistance. Overexpression of miR-200a protected tumor cells from anoikis and promoted metastases in vivo. Furthermore, knockdown of YAP1 phenocopied the effects of miR-200a overexpression, whereas restoration of YAP1 in miR-200a overexpressed breast cancer cells reversed the effects of miR-200a on anoikis and metastasis. Remarkably, we found that YAP1 expression was inversely correlated with miR-200a expression in breast cancer clinical specimens, and miR-200a expression was associated with distant metastasis in patients with breast cancer.
  
  
  CONCLUSIONS
  Our data suggest that miR-200a functions as anoikis suppressor and contributes to metastasis in breast cancer.
authors: Breast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors: San-Jian
authors: SJ
authors: Yu
authors: Jing-Ying
authors: JY
authors: Hu
authors: Xia-Ying
authors: XY
authors: Kuang
authors: Jian-Min
authors: JM
authors: Luo
authors: Yi-Feng
authors: YF
authors: Hou
authors: Gen-Hong
authors: GH
authors: Di
authors: Jiong
authors: J
authors: Wu
authors: Zhen-Zhou
authors: ZZ
authors: Shen
authors: Hou-Yan
authors: HY
authors: Song
authors: Zhi-Ming
authors: ZM
authors: Shao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D023102:Anoikis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human