COMMD7 is correlated with a novel NF-κB positive feedback loop in hepatocellular carcinoma.

Abstract	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.
Authors	Lu Zheng, Chang-Lin Deng, Liang Wang, Xiao-Bing Huang, Nan You, Yi-Chen Tang, Ke Wu, Ping Liang, Na Mi, Jing Li
Journal	Oncotarget (Oncotarget) Vol. 7 Issue 22 Pg. 32774-84 (May 31 2016) ISSN: 1949-2553 [Electronic] United States
PMID	27129158 (Publication Type: Journal Article)
Chemical References	Adaptor Proteins, Signal Transducing COMMD7 protein, human NF-kappa B
Topics	Adaptor Proteins, Signal Transducing (genetics, metabolism) Adult Apoptosis Binding Sites Carcinoma, Hepatocellular (genetics, metabolism, pathology) Cell Movement Cell Proliferation Feedback, Physiological Female Gene Expression Regulation, Neoplastic Hep G2 Cells Humans Liver Neoplasms (genetics, metabolism, pathology) Male Middle Aged NF-kappa B (genetics, metabolism) Neoplasm Invasiveness Promoter Regions, Genetic RNA Interference Signal Transduction Time Factors Transcription, Genetic Transcriptional Activation Transfection

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