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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. Materials and methods...

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Published in:The Journal of surgical research 2014-05, Vol.188 (1), p.129-136
Main Authors: Zhou, Jing, MD, Tao, Yimin, MD, Peng, Chen, MD, Gu, Peng, MD, Wang, Wei, MD, PhD
Format: Article
Language:English
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Summary: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. Materials and 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.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2013.12.006