期刊
ONCOTARGET
卷 7, 期 38, 页码 62520-62532出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11528
关键词
long non-coding RNAs; NKILA; tongue squamous cell carcinoma; NF-kappa B; migration
资金
- Natural Science Foundation of China [81230060, 81490750, 81272951]
- Foundation for the Young Teachers in the Higher Education Institutions of China [20110171120082]
- Science Foundation of Guangdong Province [S2012030006287]
- Sun Yat-sen University Training Project Grants [13ykpy27, 14ykpy20]
- Special Project on New Drug Innovation of Sun Yat-sen University
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen Uthversity [KLB09001]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013] 163]
- Guangdong Science and Technology Department [2015B050501004]
- Translational medicine public platform of Guangdong Province [4202037]
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 I kappa Ba and NF-kappa B activation as well as the induction of the epithelial-mesenchymal transition (EMT) process. Ectopic expression of NKILA in Tscca cells inhibits NF-kappa B activator TNF-a-promoted cell migration and invasion, while applying NF-kappa B 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-kappa B 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.
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