title: MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets.
abstract: BACKGROUND
  Increasing evidence indicates that Epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). MiR-449a is a liver abundant miRNA. However, the role of miR-449a in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown.
  
  
  METHODS
  The expression levels of miR-449a were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect and underlying molecular mechanisms of miR-449a were examined further.
  
  
  RESULTS
  In the present study, we found that miR-449a was significantly decreased in HCC cells and tissues, especially in those with the portal vein tumor thrombus. In HCC cell lines, stable overexpression of miR-449a was sufficient to inhibit cell motility in vitro, and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-449a in HCC cells promoted the expression of epithelial markers and reduced the levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-449a attenuated the downstream signaling of Met, and consequently reduced the accumulation of Snail in cell nucleus by targeting the 3'-untranslated regions (3'-UTR) of FOS and Met.
  
  
  CONCLUSIONS
  Our data highlight an important role of miR-449a in the molecular etiology of HCC, and implicate the potential application of miR-449a in cancer therapy.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang West Road, Guangzhou, 510120, China. chenshp@sysucc.org.cn.|The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, No. 651, Dongfeng Road East, Guangzhou, China. chenshp@sysucc.org.cn.
authors.forename: Shu-Peng
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Department of orthopedics, Guangzhou hospital of traditional Chinese medicine, No. 16, Zhuji Road, Guangzhou, China. liubaoxin898@163.com.
authors.forename: Bao-Xin
authors.initials: BX
authors.lastname: Liu
authors.affiliation: Department of Pathology, Guangdong Provincial People's Hospital, No.107, Zhongshan Er Road, Guangzhou, China. ougoug@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, the Fifth Affiliated Hospital, Sun Yat-sen University, No. 57, Meihua East Road, Zhuhai, China. 13923381037@139.com.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Pei
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, No. 651, Dongfeng Road East, Guangzhou, China. liaoyj@sysucc.org.cn.
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.affiliation: Department of Breast Surgery, Hubei Provincial Cancer Hospital, No. 116, Zhuodaoquan South Road, Wuhan, China. wqdyu_yf@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107, Yanjiang West Road, Guangzhou, 510120, China. effortgreatlylty@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C544530:MIRN449 microRNA, human; D035683:MicroRNAs