title: miR-503 regulates metastatic function through Rho guanine nucleotide exchanger factor 19 in hepatocellular carcinoma.
abstract: BACKGROUND
  Our previous work described a metastasis-related microRNAs expression profiling and revealed miR-503 regulating metastatic function in hepatocellular carcinoma (HCC) cells. Here, we investigate to define the mechanism of miR-503 regulating metastasis in HCC.
  
  
  METHODS
  The expressions of miR-503 in HCC cell lines and clinical tissues with different metastatic potential were investigated. Meanwhile, a metastatic human HCC cell BALB/c nude mice model was used to investigate whether miR-503 regulates metastasis of HCC in vivo. Furthermore, luciferase activity of reporter gene, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence-activated cell sorting analysis (FACS), and invasion assay were carried out to characterize the mechanism of miR-503 regulating metastasis in HCC.
  
  
  RESULTS
  We confirmed the negative correlation between miR-503 expression and metastatic potential of HCC in cell lines and in clinical HCC tissues. We also showed that overexpression of miR-503 resulted in inhibition of proliferation and metastasis of HCC in vivo. Furthermore, we demonstrated that ARHGEF19 is a direct target gene of miR-503. Finally, our results indicated that ARHGEF19 overcomes the suppressive influence of miR-503 in HCC cells.
  
  
  CONCLUSIONS
  Our results suggest an important role of miR-503 in inhibiting metastasis of HCC through deregulating ARHGEF19.
authors.affiliation: Department of Stomatolog, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: wangweicsu@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D016086:Lentivirus; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: C000588578:ARHGEF19 protein, human; D020662:Guanine Nucleotide Exchange Factors; C545473:MIRN503 microRNA, human; D035683:MicroRNAs
keywords: ARHGEF19; Hepatocellular carcinoma; Metastasis; RhoC; miR-503