You Nan, Li Jing, Huang Xiaobing, Wu Ke, Tang Yichen, Wang Liang, Li Hongyan, Mi Na, Zheng Lu
Department of Hepatobiliary Surgery, Xinqiao Hospital of Third Military Medical University, Chongqing 400037, China.
Department of Hepatobiliary Surgery, Xinqiao Hospital of Third Military Medical University, Chongqing 400037, China.
Biomed Pharmacother. 2017 Apr;88:653-657. doi: 10.1016/j.biopha.2017.01.046. Epub 2017 Jan 29.
Hepatocellular carcinoma (HCC) is still a heavy threat to public health. However, novel therapeutic and diagnostic method for HCC is still urgently needed thus far. Based on sequence analysis and homology comparison, we previously reported a novel gene termed COMMD7, which is mapped to 20q11.22 and promotes cell proliferation in HCC cells. But the molecular mechanisms underlying the pro-tumor property of COMMD7 are not fully addressed yet. In this study, we demonstrate that the conditional medium derived from COMMD7-overexpressed HCC cell promotes proliferation of naïve HCC cells. The over-expression of COMMD7 significantly induced the migratory and invasive in HCC cells. Mechanistic study found that over-expression of COMMD7 induces C-X-C motif chemokine 10 (CXCL10) expression. Blocking CXCL10 signal transduction by neutralizing antibody abolished COMMD7-mediated cell proliferation and migration. In conclusion, COMMD7 promotes hepatocellular carcinoma through regulating CXCL10. The present data suggests a potential role of CXCL10 in the oncogenic function of COMMD7, and will lead to a better understanding of the development of HCC.
肝细胞癌（HCC）仍然对公众健康构成重大威胁。然而，迄今为止，仍迫切需要针对HCC的新型治疗和诊断方法。基于序列分析和同源性比较，我们之前报道了一个名为COMMD7的新基因，它定位于20q11.22，并促进HCC细胞的增殖。但是，COMMD7促肿瘤特性背后的分子机制尚未完全阐明。在本研究中，我们证明源自COMMD7过表达的HCC细胞的条件培养基可促进未处理的HCC细胞的增殖。COMMD7的过表达显著诱导HCC细胞的迁移和侵袭。机制研究发现，COMMD7的过表达诱导C-X-C基序趋化因子10（CXCL10）的表达。用中和抗体阻断CXCL10信号转导可消除COMMD7介导的细胞增殖和迁移。总之，COMMD7通过调节CXCL10促进肝细胞癌。目前的数据表明CXCL10在COMMD7的致癌功能中具有潜在作用，并将有助于更好地理解HCC的发生发展。
