Wang Peng, Cao Jia, Liu Shihai, Pan Huazheng, Liu Xiangping, Sui Aihua, Wang Liping, Yao Ruyong, Liu Zimin, Liang Jun
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
Clinical medicine college, Ningxia Medical University, Ningxia, P.R. China.
Oncol Rep. 2017 May;37(5):2883-2890. doi: 10.3892/or.2017.5507. Epub 2017 Mar 15.
Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. however, its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that miR-429 was significantly downregulated in HCC tissue samples and cell lines. Upregulation of miR-429 markedly suppressed proliferation and migration of HCC cells. Moreover, we identified TRAF6 as a direct target of miR-429. Downregulation of TRAF6 partially attenuated the oncogenic effect of anti‑miR-429 on HCC cells. Ectopic expression of miR-429 in HCC cells inhibited TCF-4 activity as well as nuclear accumulation of P65 and expression of the NF-κB targets c-Myc and phosphorylation of TAK1. In a nude xenograft model, miR-429 upregulation significantly decreased HCC growth. In conclusion, by targeting TRAF6, miR-429 is downregulated in HCC and inhibits HCC cell proliferation and motility. Our data suggest that miR-429 may serve as a potential anticancer target for the treatment of HCC.
越来越多的证据表明，miR-429在多种人类癌症中发挥肿瘤抑制作用。然而，其在肝细胞癌（HCC）中的作用仍不清楚。在本研究中，我们发现miR-429在HCC组织样本和细胞系中显著下调。miR-429的上调显著抑制了HCC细胞的增殖和迁移。此外，我们确定TRAF6是miR-429的直接靶点。TRAF6的下调部分减弱了抗miR-429对HCC细胞的致癌作用。miR-429在HCC细胞中的异位表达抑制了TCF-4活性以及P65的核积累和NF-κB靶标c-Myc的表达及TAK1的磷酸化。在裸鼠异种移植模型中，miR-429的上调显著降低了HCC的生长。总之，通过靶向TRAF6，miR-429在HCC中下调并抑制HCC细胞的增殖和运动。我们的数据表明，miR-429可能作为治疗HCC的潜在抗癌靶点。
