Long noncoding RNA NKILA enhances the anti-cancer effects of baicalein in hepatocellular carcinoma via the regulation of NF-κB signaling

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancer and leading cause of cancer-related death worldwide. Baicalein, a principle flavonoid, has shown attractive anti-cancer effects on HCC. However, the underlying molecular mechanisms and influencing factors contributing to the anti-cancer effects of baicalein on HCC are still largely unknown. Long noncoding RNAs (lncRNAs) have been revealed to be fascinating therapeutic targets for cancers. The roles of NF-κB Interacting LncRNA (NKILA) are recently explored in several cancers. However, the expressions, clinical significances, roles and action mechanisms of NKILA in the anti-cancer effects of baicalein on HCC are unknown. In this study, we found that NKILA is down-regulated in HCC and reduced expression of NKILA indicts poor survival of HCC patients. Functional assays showed that overexpression of NKILA enhances the roles of baicalein on HCC cell proliferation inhibition, apoptosis induction, and migration inhibition in vitro and tumor growth suppression in vivo. Conversely, knockdown of NKILA suppresses the effects of baicalein. Mechanistically, we found that NKILA inhibits IκBα phosphorylation, NF-κB nuclear translocation, and NF-κB activity. NKILA also enhances the inhibitory effects of baicalein on NF-κB signaling. Furthermore, the effects of NKILA on baicalein-induced NF-κB activity inhibition, cell growth inhibition, apoptosis induction, and migration inhibition are reversed by NF-κB nuclear translocation inhibitor JSH-23. Collectively, our data demonstrated that NKILA enhances the anti-cancer effects of baicalein on HCC in vitro and in vivo via the regulation of NF-κB signaling, and implied that the combination of NKILA and baicalein would be potential therapeutic strategies for HCC.