title: MicroR-760 suppresses cancer stem cell subpopulation and breast cancer cell proliferation and metastasis: By down-regulating NANOG.
abstract: OBJECTIVE
  Emerging evidences suggest that cancer stem cells are responsible for tumor aggressive, metastasis and therapeutic resistance. To data, the mechanism underlying breast cancer stem cell (BCSC) population within tumor metastasis remains to be fully elucidated. The current study was to investigate the potential role of microRNA-760 (miR-760) and its associated target gene in population and metastasis of BCSC.
  
  
  METHODS
  Characteristic BCSCs surface markers (CD44(+)/CD24(-/low)) were determined by flow cytometry in breast cancer MCF-7 and BT-549 cells. Quantitative RT-PCR was used to evaluate miR-760 and NANOG mRNA expression. Expression of NANOG protein was determined using western blot. Cell proliferation was determined by MTT assay. The model of breast cancer cell xenograft was used to evaluate the effect of miR-760 on tumor growth.
  
  
  RESULTS
  BT-549 cell has substantially more CD44(+)/CD24(-/low) subpopulation than MCF-7 cell. Moreover, BT-549 cell expressed lower level of miR-760 and higher level of NANOG than MCF-7cell. By result from cellular miR-760 modulation, we found that miR-760 overexpression suppressed CD44(+)/CD24(-/low) population as well as inhibited cell proliferation and migration of BT-549. On the contrary, knockdown of miR-760 promoted CD44(+)/CD24(-/low) population and migration of MCF-7 cells. By luciferase reporter assay, miR-760 was proved to be functional associated with NANOG via regulating its expression. This functional interaction was showed to be involved in controlling proliferation and migration of MCF-7 and BT-549 cell.
  
  
  CONCLUSIONS
  These data suggest that the target of miR-760/NANOG axis may represent a new therapeutic approach to suppress breast cancer stem cell subpopulation thereby prevent cancer metastasis.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Han
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; The Key Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Gu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Pei
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; The Key Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Guang-Cheng
authors.initials: GC
authors.lastname: Guo
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; The Key Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zhu
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, 1st Jian She Dong Road, Zhengzhou 450052, China. Electronic address: wangyimeng158@163.com.
authors.forename: Yi-Meng
authors.initials: YM
authors.lastname: Wang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071317:Nanog Homeobox Protein / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015703:Antigens, CD; C579293:MIRN760 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein
keywords: BT-549; Breast cancer stem cell; MCF-7; NANOG; miR-760