Zheng Lu, Deng Chang-Lin, Wang Liang, Huang Xiao-Bing, You Nan, Tang Yi-Chen, Wu Ke, Liang Ping, Mi Na, Li Jing
Department of Hepatobiliary Surgery, Xinqiao Hospital of Third Military Medical University, Chongqing, 400037, China.
Oncotarget. 2016 May 31;7(22):32774-84. doi: 10.18632/oncotarget.9047.
The correlation between nuclear factor-kappa B (NF-κB) and COMMD7 in hepatocellular carcinoma (HCC) development remained unclear. Here, our clinicopathological data showed that COMMD7 is overexpressed in HCC with a correlation to NF-κB. Using HepG2 and SMMC-7721 cells that aberrantly overexpressed COMMD7, we found that NF-κB directly binds with COMMD7 promoter and serves as an activator for COMMD7 transcription by luciferase reporter assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). In both HepG2 cells and SMMC-7721 cells, the silencing of COMMD7 significantly inhibited the cell proliferation, whereas NF-κB silencing inhibited the expression of COMMD7 and further inhibited cell proliferation. In addition, cell apoptosis was promoted by COMMD7 silencing, and further promoted by NF-κB silencing. Cell migration and invasion were also inhibited by COMMD7 silencing, and further inhibited by NF-κB silencing. Thus, COMMD7 is correlated with a novel NF-κB positive feedback loop in hepatocellular carcinoma. Developing strategies for the treatment of HCC should consider the correlation between NF-κB and COMMD7, so as to improve the specificity and sensitivity of therapy and to reduce toxicity.
核因子-κB（NF-κB）与COMMD7在肝细胞癌（HCC）发生发展中的相关性仍不清楚。在此，我们的临床病理数据显示，COMMD7在HCC中过表达，且与NF-κB相关。通过使用异常过表达COMMD7的HepG2和SMMC-7721细胞，我们发现NF-κB直接与COMMD7启动子结合，并通过荧光素酶报告基因检测、染色质免疫沉淀（ChIP）和电泳迁移率变动分析（EMSA）作为COMMD7转录的激活剂。在HepG2细胞和SMMC-7721细胞中，COMMD7的沉默均显著抑制细胞增殖，而NF-κB沉默则抑制COMMD7的表达并进一步抑制细胞增殖。此外，COMMD7沉默促进细胞凋亡，NF-κB沉默则进一步促进细胞凋亡。COMMD7沉默也抑制细胞迁移和侵袭，NF-κB沉默则进一步抑制细胞迁移和侵袭。因此，COMMD7与肝细胞癌中一种新的NF-κB正反馈环相关。开发HCC治疗策略应考虑NF-κB与COMMD7之间的相关性，以提高治疗的特异性和敏感性并降低毒性。
