title: Hsa-miR-206 represses the proliferation and invasion of breast cancer cells by targeting Cx43.
abstract: OBJECTIVE
  Hsa-miR-206, a microRNA, was found to be able to switch subtypes by targeting ER-α in breast cancer. However, there are few studies addressing the role of miR-206 in triple-negative breast cancer (TNBC). The purpose of this study was to evaluate the metastatic-regulatory ability of miR-206 in TNBC.
  
  
  METHODS
  We treated two TNBC lines (MDA-MB-231 and MDA-MB-436) with miR-206 mimics, inhibitors and paired controls and examined the in vitro and in vivo functions of miR-206 via the degradation of Connexin43 (Cx43). A luciferase reporter assay was used to identify the binding site of GJA1 (gap junctional intercellular communication) (Cx43) and miR-206. Furthermore, quantitative RT-PCR was used to evaluate miR-206 expression in 77 breast cancer samples to determine the association with lymph node status and Cx43 expression.
  
  
  RESULTS
  Up-regulation of miR-206 in TNBC contributed to a decreasing metastatic potential, as demonstrated by a reduction of cell viability and proliferation, decreased cell migration and invasion, lower expression levels of matrix metalloproteinase (MMP)-2, MMP-9 and a higher expression level of breast cancer metastatic suppressor (BRMS)-1. In vitro dual luciferase assays showed GJA1 (Cx43) is a target of miR-206. Quantitative RT-PCR was conducted to evaluate miR-206 expression in 77 breast cancer samples to determine the associations between miR-206 levels and both lymph node status and Cx43 expression. Restoring Cx43 expression positively regulated cell adhesion and GJA1, which may facilitate metastasis. MiR-206 significantly attenuated the proliferation and metastatic potential of cancer cells but did not inhibit tumor onset in a mouse xenograft model because of the dual function of Cx43.
  
  
  CONCLUSIONS
  Our results suggest hsa-miR-206 may repress the tumor proliferation and invasion in breast cancer by targeting Cx43.
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China. zhuang_zg@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Shao
authors.forename: Q-Z
authors.initials: QZ
authors.lastname: He
authors.forename: B-Q
authors.initials: BQ
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018031:Connexin 43 / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C500216:GJA1 protein, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9