Abstract
Long non-coding RNAs (lncRNAs) have emerged recently as key regulators of tumor development and progression. Our previous study identified an NF-KappaB interacting lncRNA (NKILA) which was negatively correlated with breast cancer metastasis and patient prognosis. However, its clinical significance and potential role in Tongue squamous cell carcinoma (TSCC) remain unclear. Here we show that NKILA is down-regulated in TSCC cancer tissues than that in matched adjacent noncancerous tissues. And low NKILA expression in TSCC is significantly correlated with tumor metastasis and poor patient prognosis. In vitro, overexpression of NKILA decreases TSCC cells migration and invasion. Mechanistic study shows that NKILA inhibits the phosphorylation of IκBα and NF-κB activation as well as the induction of the epithelial-mesenchymal transition (EMT) process. Ectopic expression of NKILA in Tscca cells inhibits NF-κB activator TNF-α-promoted cell migration and invasion, while applying NF-κB inhibitor Bay-117082 or JSH-23 in NKILA silenced CAL27 cells reverses cell migration capacity to lower level. In vivo experimental metastasis model also demonstrates NKILA inhibits lung metastasis of NOD/SCID mice with TSCC tumors. These results suggested that NKILA is a vital determinant of TSCC migration and invasion and NF-κB signaling pathway mediates this effect. Given the above mentioned function of NKILA, it could act as a potential predictor for overall survival in patients with TSCC and a potential therapeutic target for TSCC intervention.
Highlights
Tongue squamous cell carcinoma (TSCC) is the most common epithelial cancer identified in the oral cavity [1]
We aimed to investigate the role of NF-KappaB interacting lncRNA (NKILA) in regulating the Nuclear factor-κB (NF-κB) activity, tumor cell epithelial-mesenchymal transition (EMT) and metastasis in TSCC, as well as the clinical significance of NKILA in predicting tumor metastasis and patient prognosis
Our previous report suggested the reduced NKILA is associated with clinical invasion and metastasis of breast cancer [13]
Summary
Tongue squamous cell carcinoma (TSCC) is the most common epithelial cancer identified in the oral cavity [1]. Nuclear factor-κB (NF-κB) is a family of transcription factors that play critical roles in multiple physiological and pathological processes including inflammation, immunity, cell proliferation, differentiation, and survival [3]. EMT is a common morphologic transformation in cancer cells that causes loss of cell-cell adhesion and increases cell motility which plays an important role in tumor progression and metastasis [7]. A serial of transcriptional repressors, such as Zeb-1/2, Twist, Snail, and Slug control the EMT process by recruiting histone deacetylases to the E-box elements of E-cadherin promoter, leading to transcriptional silence of E-cadherin expression [8]. NF-κB was reported to binds to the promoters of the E-cadherin repressor genes and regulates the EMT phenotype and migration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
