title: miR-200b and miR-200c as prognostic factors and mediators of gastric cancer cell progression.
abstract: OBJECTIVE
  The purpose of this study was to investigate the clinicopathologic significance and potential role of miR-200b and miR-200c in the development and progression of gastric cancer.
  
  
  METHODS
  We examined miR-200b and miR-200c expression in 36 paired normal and stomach tumor specimens, as well as gastric cancer cell lines, by quantitative real-time PCR. In addition, miR-200b and miR-200c were detected by ISH using gastric cancer tissue microarrays, and the association between miR-200b and miR-200c levels and clinicopathologic factors and prognosis were analyzed. A luciferase assay was conducted for target evaluation. The functional effects of miR-200b and miR-200c on gastric cancer cells were validated by a cell proliferation assay and cell invasion and migration assays.
  
  
  RESULTS
  miR-200b and miR-200c were downregulated in the gastric cancer specimens and cell lines tested. miR-200b and miR-200c levels were significantly correlated with the clinical stage, T stage, lymph node metastasis, and survival of patients. Ectopic expression of miR-200b and miR-200c impaired cell growth and invasion. In addition, when overexpressed, miR-200b and miR-200c commonly directly targeted DNMT3A, DNMT3B, and SP1 (a transactivator of the DNMT1 gene), which resulted in marked reduction of the expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B at the protein level. This effect, in turn, led to a decrease in global DNA methylation and reexpression of p16, RASS1A1, and E-cadherin via promoter DNA hypomethylation.
  
  
  CONCLUSIONS
  Our findings suggest that miR-200b and miR-200c, as valuable markers of gastric cancer prognosis, may be a promising approach to human gastric cancer treatment.
authors.affiliation: Authors' Affiliations: Department of Breast Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center; Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, Guangdong; and Cancer Research Institute, University of South China, Hengyang, Hunan, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Tang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xie
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Guo
authors.forename: Yanan
authors.initials: Y
authors.lastname: Kong
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D020029:Base Pairing; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D015820:Cadherins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C533896:MIRN200 microRNA, human; C411762:RASSF1 protein, human; C000619380:DNMT1 protein, human