Upregulated microRNA-429 inhibits the migration of HCC cells by targeting TRAF6 through the NF-κB pathway
Upregulated microRNA-429 inhibits the migration of HCC cells by targeting TRAF6 through the NF-κB pathway
复制标题
上调的 microRNA-429 通过 NF-kappa B 通路靶向 TRAF6 抑制 HCC 细胞的迁移
DOI：
10.3892/or.2017.5507
复制
发表时间：
2017-05-01
期刊：
影响因子：
4.2
通讯作者：
Liang, Jun
中科院分区：
文献类型：
--
作者：
Wang, Peng;Cao, Jia;Liang, Jun
越来越多的证据表明，miR-429参与多种人类癌症的肿瘤抑制。然而，其在肝细胞癌（HCC）中的作用尚不清楚。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。上调miR-429可显著抑制HCC细胞的增殖和迁移。此外，我们发现TRAF6是miR-429的直接靶点。下调TRAF6可部分减弱anti-miR-429对HCC细胞的致癌作用。HCC细胞中miR-429的异位表达抑制了TCF-4活性、P65的核积累、NF-kappa B靶点c-Myc的表达和TAK1的磷酸化。在裸体异种移植模型中，miR-429上调可显著降低HCC的生长。总之，通过靶向TRAF6， miR-429在HCC中下调，抑制HCC细胞的增殖和运动。我们的数据表明，miR-429可能作为HCC治疗的潜在抗癌靶点。
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-kappa B 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.