Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell carcinoma cells via suppressing epithelial-mesenchymal transition.
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.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Wei
W
Huang
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Xiuying
X
Cui
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Jianing
J
Chen
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Yuhuan
Y
Feng
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Erwei
E
Song
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Jinsong
J
Li
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.|Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Yujie
Y
Liu
D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009570:Nitriles / Q000737:chemistry; D010655:Phenylenediamines / Q000737:chemistry; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000378:metabolism*; D013450:Sulfones / Q000737:chemistry; D014062:Tongue Neoplasms / Q000473:pathology*
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C549066:4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine; D016328:NF-kappa B; D009570:Nitriles; D010655:Phenylenediamines; D062085:RNA, Long Noncoding; D013450:Sulfones; C000625507:long noncoding RNA NKILA, human
NF-κB; NKILA; long non-coding RNAs; migration; tongue squamous cell carcinoma