NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition

• Published in: PLoS genetics Vol. 15; no. 8; p. e1008325
• Main Authors: Zhang, Wei, Guo, Qiannan, Liu, Guoying, Zheng, Fang, Chen, Jianing, Huang, Di, Ding, Linxiaoxiao, Yang, Xing, Song, Erwei, Xiang, Yanqun, Yao, Herui
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-08-2019; Public Library of Science (PLoS)
• Subjects: Apoptosis; Biology and life sciences; Breast cancer; Carcinogenesis; Carcinogenesis - genetics; Cell Line, Tumor; Cell survival; Cytokines; Epigenetics; Fang Zheng; Female; Funding; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Invasiveness; Kaplan-Meier Estimate; Laboratories; Male; Medical prognosis; Medicine and Health Sciences; Metastases; Metastasis; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - mortality; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - mortality; Nasopharyngeal Neoplasms - pathology; Nasopharynx - pathology; NF-kappa B - metabolism; NF-κB protein; Non-coding RNA; Oncology; Paraffin; Phosphorylation; Prognosis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-mediated interference; Signal Transduction - genetics; Supervision; Throat cancer; China
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008325

The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired para-cancerous tissues. NKILA was identified as a potential functional lncRNA by this lncRNA expression profile. We used 107 paraffin-embedded NPC tissues with different TNM stages to detect the expression of NKILA and analyzed the survival data by Log-rank test and Cox regression. The role of NKILA and its underlying mechanisms in the progression of NPC were evaluated by a series of experiments in vitro and vivo by silencing or expressing NKILA. Compared with control tissues, NKILA expression was identified to be decreased in NPC tissues. Low NKILA expression was correlated with unfavorable clinicopathological features and predicted poor survival outcome in NPC patients. After adjusting for potential confounders, low expression of NKILA was confirmed to be an independent prognostic factor correlated with poor survival outcomes. Furthermore, we found that NKILA overexpression in high-metastatic-potential NPC cells repressed motile behavior and impaired the metastatic capacity in vitro and in vivo. In contrast, RNAi-mediated NKILA depletion increased the invasive motility of cells with lower metastatic potential. Further experiments demonstrated that NKILA regulated the metastasis of NPC through the NF-κB pathway. Taken together, NKILA plays vital roles in the pathogenesis of NPC. The unique histological characteristics of NPC indicate that local inflammation plays a vital role in carcinogenesis of nasopharyngeal carcinoma.