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Mol Ther Oncolytics. 2018 Dec 14;12:112-123. doi: 10.1016/j.omto.2018.12.006. eCollection 2019 Mar 29.

COMMD7 Regulates NF-κB Signaling Pathway in Hepatocellular Carcinoma Stem-like Cells.

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1
Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Army Medical University, PLA, Chongqing, China.

Abstract

Previous studies showed that the COpper Metabolism gene MURR1 Domain (COMMD) family of proteins was abnormally expressed in hepatocellular carcinoma (HCC). This study aimed to explore the roles of COMMD1 and COMMD7 in regulating nuclear factor κB (NF-κB) signaling in HCC stem cells (HCSCs). In vivo, the expression of COMMD7 and COMMD1 was determined in 35 pairs of HCC cancer tissues and adjacent tissues, and the effect of COMMD7 silencing on xenograft tumor growth was evaluated. In vitro, the effects of COMMD7 silencing and COMMD1 overexpression on HCSC function were assessed. Results found that the expression levels of COMMD7 were higher, whereas COMMD1 levels were lower in HCC tissues and HCSCs. COMMD7 silencing or COMMD1 overexpression inhibited cell proliferation, migration, and invasion through suppression of NF-κB p65. Furthermore, COMMD7 positively regulated NF-κB by upregulating protein inhibitor for activated stat 4 (PIAS4). This study demonstrates that COMMD7 has a dual regulatory role in the NF-κB signaling pathway in Nanog+ HCSCs.

KEYWORDS:

cancer stem cells; hepatocellular carcinoma; tumorigenicity

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