COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

You,Nan; Li,Jing; Huang,Xiaobing; Wu,Ke; Tang,Yichen; Wang,Liang; Li,Hongyan; Mi,Na; Zheng,Lu

doi:10.3892/mmr.2018.8706

COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

Authors:
- Nan You
- Jing Li
- Xiaobing Huang
- Ke Wu
- Yichen Tang
- Liang Wang
- Hongyan Li
- Na Mi
- Lu Zheng
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Affiliations: Department of Hepatobiliary Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, P.R. China
Published online on: March 8, 2018 https://doi.org/10.3892/mmr.2018.8706
Pages: 6784-6788

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Abstract

While >80% of the incidence occurs in sub‑Saharan Africa and East Asia, cases of hepatocellular carcinoma (HCC) have been rapidly increasing in Western countries. Despite its global importance, HCC is relatively under‑researched compared with other lethal cancer types, which is possibly due to the high complexity and heterogeneity of HCC. It has been reported previously that COMM domain‑containing protein 7 (COMMD7) is upregulated in HCC and promotes HCC cell proliferation by triggering C‑X‑C motif chemokine 10 (CXCL10) production. However, the value of targeting CXCL10 signal transduction in treating COMMD7‑positive tumors, or the molecular mechanisms underlying COMMD7‑mediated CXCL10 expression, has not been completely addressed. In the present study, it was demonstrated that disruption of the CXCL10/C‑X‑C chemokine receptor type 3 axis reduces COMMD7‑mediated HCC cell proliferation. Furthermore, COMMD7 modulates CXCL10 production by activating nuclear factor (NF)‑κB. Additionally, it was demonstrated that intracellular reactive oxygen species (ROS) are required for NF‑κB activation and CXCL10 production. In conclusion, COMMD7 activates CXCL10 production by regulating NF‑κB and the production of ROS. The present study highlighted the role of COMMD7 in the development of HCC, and provides novel options for anticancer drug design.

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