Reduced IκBα promotes hepatocellular carcinoma cell proliferation and migration via regulation of NF-κB/Erbin axis.

Aberrantly low expression of NF-kappa B inhibitor alpha (I kappa B alpha) is observed in hepatocellular carcinoma (HCC), yet the underlying mechanism via which I kappa B alpha regulates HCC remains largely unknown. Therefore, to determine the potential function of I kappa B alpha in hepatocarcinogenesis, the present study used immunohistochemistry (IHC) staining to analyze the associations between I kappa B alpha protein expression and clinicopathologic characteristics of 107 patients with HCC. It was found that expression of I kappa B alpha was significantly associated with tumor recurrence. Moreover, I kappa B alpha protein expression was decreased in 107 HCC tissue samples and was positively associated with overall survival. Mechanistically, it was demonstrated that silencing of I kappa B alpha activated NF-kappa B in both Huh7 and HCCLM3 cells, followed by upregulation of Erbb2 interacting protein (Erbin) at both the mRNA and protein levels, confirmed by reverse transcription-quantitative PCR and western blotting, to promote cell proliferation and migration. Furthermore, knockdown of Erbin significantly attenuated NF-kappa B-mediated cell proliferation and migration. It was also identified that overexpression of Erbin in HCC tissues promoted both cell proliferation and migration, and was negatively associated with I kappa B alpha expression in 107 HCC tissue samples. Thus, these results indicated that downregulation of I kappa B alpha promoted HCC tumorigenesis via upregulation of NF-kappa B-mediated Erbin expression.