1. Expression of Concern: NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition
- Subjects
Carcinogenesis ,Physiology ,Immunology ,Apoptosis ,Pathology and Laboratory Medicine ,Carcinomas ,Biochemistry ,Metastasis ,Signs and Symptoms ,Diagnostic Medicine ,Immune Physiology ,Basic Cancer Research ,otorhinolaryngologic diseases ,Medicine and Health Sciences ,Post-Translational Modification ,Phosphorylation ,Non-coding RNA ,Immune Response ,Inflammation ,Innate Immune System ,Nasopharyngeal Carcinoma ,Biology and life sciences ,Cell Death ,Cancers and Neoplasms ,Proteins ,Cell Biology ,Molecular Development ,Nucleic acids ,stomatognathic diseases ,Oncology ,Cell Processes ,Immune System ,Long non-coding RNAs ,RNA ,Cytokines ,Research Article ,Developmental Biology - Abstract
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., Author summary NF-κB is a pivotal link between NPC and inflammation. Importantly, NF-κB was found to be overexpressed in nearly all NPC tissues, and inflammatory cytokines have also been observed in NPC tissues. Inflammatory cytokines promote the susceptibility of NPC cells to metastasize via constant NF-κB activation. Here, we found that NKILA, a newly identified lncRNA, is upregulated by inflammatory cytokines and is significantly downregulated in NPC. By a series of in vitro and in vivo experiments, we show that NKILA exerts its effect as a tumor suppressor via inhibiting tumorigenesis and metastasis of NPC. Further studies indicate that NKILA regulates the metastasis of NPC through NF-κB pathway. Our research demonstrates that NKILA plays a critical role in the progression of NPC. These findings are particularly important as they provide new insights into the effects of inflammation on the biology of NPC. NKILA might be a candidate molecular marker and a novel therapy target for NPC patients.
- Published
- 2022