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

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.

Up-regulated long non-coding RNA ILF3-AS1 indicates poor prognosis of nasopharyngeal carcinoma and promoted cell metastasis

“…5,20 lncRNA NKILA could suppress NPC carcinogenesis and metastasis through regulating the NF-κB pathway. 21 lncRNA FAM225A promotes NPC development and invasion by increasing the ITGB3 level via miR-590-3p/miR-1275. 22 lncRNA PVT1 regulates the growth of NPC cells by HIF-1α stability and KAT2A acetyltransferase activation, while lncRNA LOC284454 promotes NPC cell invasion and migration via the Rho/Rac signaling pathway.…”

Long non-coding RNA NKILA weakens TNF-α-induced inflammation of MRC-5 cells by miR-21 up-regulation

“…In recent years, the research explored the role of NKILA in cancer. Studies presented NKILA restrained nasopharyngeal carcinoma metastatic potential [23] and could be a diagnosis and prognosis marker of colorectal cancer [24]. Although the specific intrinsic mechanism had not been fully elucidated, studies have confirmed that NKILA played an important role in inflammation.…”

Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma

“…NKILA has been reported to suppress NF-κB signaling pathway by blocking IkBα phosphorylation in breast cancer, non-small cell lung cancer and nasopharyngeal carcinoma [19][20][21]. To elucidate NKILA function in lymphoma, NKILA-targeted siRNA was used to knock down NKILA and non-targeting siRNA was used as a control in SU-DHL-1.…”