NKILA, a prognostic indicator, inhibits tumor metastasis by suppressing NF-κB/Slug mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

The metastasis of hepatocellular carcinoma (HCC) is one of the major obstacles hindering its therapeutic efficacy, leading to low surgical resection rate, high mortality and poor prognosis. Accumulating evidence has shown that both long noncoding RNA (lncRNA) and NF-κB play vital roles in the regulation of cancer metastasis. However, the clinical significance and biological function of NKILA (NF-κB interacting lncRNA) and its interaction with NF-κB in HCC remain unknown. In this study, we demonstrated that NKILA was down-regulated in HCC tissues and cell lines, and decreased NKILA expression was significantly associated with larger tumor size and positive vascular invasion in HCC patients. NKILA reduction was an independent risk factor of HCC patients' poor prognosis, and the 5-year overall survival (OS) rates of patients with low and high NKILA expression were 15.6% and 60.0%, respectively. Moreover, NKILA inhibits migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NKILA prevents Slug/epithelial to mesenchymal transition (EMT) pathway via suppressing phosphorylation of IκBα, p65 nuclear translocation and NF-κB activation. In conclusion, these results indicate that NKILA might serve as an effective prognostic biomarker and a promising therapeutic target against HCC metastasis.

Chen R ，Cheng Q ，Owusu-Ansah KG ，Song G ，Jiang D ，Zhou L ，Xu X ，Wu J ，Zheng S ... -  《International Journal of Biological Sciences》

Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway.

Lu Z ，Li Y ，Wang J ，Che Y ，Sun S ，Huang J ，Chen Z ，He J ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell carcinoma cells via suppressing epithelial-mesenchymal transition.

Huang W ，Cui X ，Chen J ，Feng Y ，Song E ，Li J ，Liu Y ... -  《Oncotarget》

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

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.

Yu X ，Tang W ，Yang Y ，Tang L ，Dai R ，Pu B ，Feng C ，Xia J ... -  《-》

RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-κB-mediated epithelial-mesenchymal transition.

Song FN ，Duan M ，Liu LZ ，Wang ZC ，Shi JY ，Yang LX ，Zhou J ，Fan J ，Gao Q ，Wang XY ... -  《PLoS One》