title: miR-449a targets Flot2 and inhibits gastric cancer invasion by inhibiting TGF-β-mediated EMT.
abstract: BACKGROUND
  Flot2, a highly conserved protein of the SPFH domain containing proteins family, has recently been identified as oncogene to be involved in the tumorigenesis and metastasis of several cancers including gastric cancer. However, the underlying molecular mechanism of Flot2 in gastric cancer (GC) is largely unknown.
  
  
  METHODS
  qRT-PCR and western blot was performed to detect miR-449a and Flot2 expression in GC cell lines and Normal human gastric epithelial cells. Then, luciferase reporter assay was used to elucidate whether Flot2 is a target gene of miR-449a. Finally, the roles and mechanism of miR-449a in regulation of tumor invasion were further investigated.
  
  
  RESULTS
  In this study, miR-449a expression was downregulated and Flot2 was upregulated in all GC cell lines as compared with that in GES-1. luciferase reporter assay identified Flot2 as a novel direct target of miR-449a. miR-449a regulated GC cell invasion by suppressing Flot2 expression. Expression analysis of a set of epithelial-mesenchymal transition (EMT) markers showed that miR-449a reduced the expression of mesenchymal markers (vimentin and N-cadherin) and induced the expression of epithelial marker (E-cadherin), which was consistent with silenced Flot2. Moreover, Flot2 is necessary for TGF-β-induced EMT in GC cells.
  
  
  CONCLUSIONS
  Our results demonstrated that miR-449a suppressed Flot2 expression results in decreased cell invasion through repressing TGF-β-mediated-EMT, and provides a new theoretical basis to further investigate miR-449a-regulated Flot2 as a potential biomarker and a promising approach for GC treatment.
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China. Liuting818@126.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China. q778342@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China. yaokkk223@163.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China. dai2113bb@163.com.
authors.forename: Aimin
authors.initials: A
authors.lastname: Leng
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China. tingliu2112a@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015820:Cadherins; C544530:MIRN449 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; C106354:flotillins