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

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)-kappa B. Additionally, it was demonstrated that intracellular reactive oxygen species (ROS) are required for NF-kappa B activation and CXCL10 production. In conclusion, COMMD7 activates CXCL10 production by regulating NF-kappa B 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.