Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Department of Breast Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, People's Republic of China.
PLoS Genet. 2019 Aug 20;15(8):e1008325. doi: 10.1371/journal.pgen.1008325. eCollection 2019 Aug.
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.
长链非编码 RNA（lncRNA）在鼻咽癌（NPC）进展中的作用尚未完全阐明。本研究旨在探讨新鉴定的 lncRNA NKILA 在 NPC 进展中的功能作用。我们使用四个 NPC 和配对的癌旁组织进行了 lncRNA 表达谱微阵列分析。通过该 lncRNA 表达谱，鉴定 NKILA 为一种潜在的功能性 lncRNA。我们使用了 107 例具有不同 TNM 分期的石蜡包埋 NPC 组织来检测 NKILA 的表达，并通过 Log-rank 检验和 Cox 回归分析生存数据。通过体外和体内一系列实验，通过沉默或表达 NKILA，评估了 NKILA 在 NPC 进展中的作用及其潜在机制。与对照组织相比，NKILA 在 NPC 组织中的表达被鉴定为降低。NKILA 低表达与不利的临床病理特征相关，并预测 NPC 患者的生存结局不良。在调整了潜在混杂因素后，证实 NKILA 低表达是与不良生存结局相关的独立预后因素。此外，我们发现 NKILA 在高转移潜能 NPC 细胞中的过表达抑制了体外和体内的迁移行为，并削弱了转移能力。相比之下，RNAi 介导的 NKILA 耗竭增加了具有较低转移潜能的细胞的侵袭迁移能力。进一步的实验表明，NKILA 通过 NF-κB 通路调节 NPC 的转移。总之，NKILA 在 NPC 的发病机制中发挥重要作用。NPC 的独特组织学特征表明局部炎症在鼻咽癌的癌变过程中起着至关重要的作用。
