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pmid28559996      Am+J+Transl+Res 2017 ; 9 (5): 2457-65
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  • MicroRNA-199a-3p inhibits tumorigenesis of hepatocellular carcinoma cells by targeting ZHX1/PUMA signal #MMPMID28559996
  • Guan J; Liu Z; Xiao M; Hao F; Wang C; Chen Y; Lu Y; Liang J
  • Am J Transl Res 2017[]; 9 (5): 2457-65 PMID28559996show ga
  • Background and objective: MicroRNAs play an important role in cell proliferation, apoptosis, differentiation, and invasion by regulating the expression of various genes. For example, the downregulation of microRNA-199a-3p (miR-199a-3p) that is noted in numerous human malignancies, including hepatocellular carcinoma (HCC), results in a poor prognosis in patients with HCC. This finding suggests that miR-199a-3p overexpression in HCC could provide a new treatment approach. We explored this possibility by examining the effects of miR-199a-3p on the growth and apoptosis of HCC cells in vitro and vivo. Methods: The miR-199a-3p signaling pathway was examined using ZHX1 (zinc-fingers and homeoboxes-1) or PUMA (a p53 upregulated modulator of apoptosis) siRNA transfection to determine the effects of miR-199a-3p on growth and apoptosis of HepG2 cells in vitro. A subcutaneously implanted tumor model of HepG2 cells in nude mice was used to assess the effects of miR-199a-3p on the signaling pathway and tumorigenesis development in vivo. Results: miR-199a-3p inhibited growth and induced apoptosis of HepG2 cells in vitro. These effects were accompanied by upregulation of ZHX1 and PUMA. Targeting ZHX1 inhibited upregulation of PUMA after miR-199a-3p transfection. In addition, miR-199a-3p inhibited Bcl2 expression, but increased Bax and cleaved caspase-3 expression. Targeting PUMA or ZHX1 reversed the effect of miR-199a-3p, followed by upregulation of Bcl2 and downregulation of Bax and cleaved caspase-3, respectively. Furthermore, miR-199a-3p inhibited tumorigenesis of xenografts in nude mice. Conclusions: miRNA-199a-3p could effectively prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related toZHX1-dependent PUMA signals.



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