NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition (Publication with Expression of Concern)
NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition (Publication with Expression of Concern)
复制标题
NKILA 通过抑制 NF-κ B 通路抑制鼻咽癌的癌变和转移
DOI：
10.1371/journal.pgen.1008325
复制
发表时间：
2019-08-01
期刊：
影响因子：
4.5
通讯作者：
Yao, Herui
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Guo, Qiannan;Yao, Herui
长非编码RNA(LncRNA)在鼻咽癌(NPC)发生发展中的作用尚未完全阐明。本研究旨在探讨NKILA这一新发现的LncRNA在鼻咽癌发生发展中的作用。我们使用四个鼻咽癌组织和配对的癌旁组织进行了LncRNA表达谱微阵列。根据这一表达谱，NKILA被鉴定为一个潜在的功能性lncRNA。对107例不同TNM分期的鼻咽癌石蜡包埋组织进行NKILA的表达检测，并对生存资料进行Log-ranch检验和Cox回归分析。通过一系列体内外实验，通过沉默或表达NKILA来评价NKILA在鼻咽癌发生发展中的作用及其机制。与对照组相比，NKILA在鼻咽癌组织中的表达降低。NKILA的低表达与鼻咽癌患者不良的临床病理特征和预后相关。在调整了潜在的混杂因素后，NKILA的低表达被确认为与不良生存结局相关的独立预后因素。此外，我们发现在高转移潜能的鼻咽癌细胞中过表达NKILA抑制了运动行为，并在体外和体内损害了转移能力。相反，RNAi介导的NKILA缺失增加了转移潜能较低的细胞的侵袭能力。进一步的实验证明，NKILA通过核因子-kappaB途径调控鼻咽癌的转移。综上所述，NKILA在鼻咽癌的发病机制中起着重要作用。鼻咽癌独特的组织学特点表明，局部炎症在鼻咽癌的发生发展中起着重要作用，而核因子-kappaB是鼻咽癌与炎症之间的关键环节。重要的是，核因子-kappaB在几乎所有的鼻咽癌组织中都有过表达，在鼻咽癌组织中也观察到了炎性细胞因子。炎性细胞因子通过持续激活核因子-kappaB，促进鼻咽癌细胞的转移。在这里，我们发现NKILA是一种新发现的lncRNA，它被炎性细胞因子上调，并在鼻咽癌中显著下调。通过一系列的体外和体内实验，我们证明NKILA通过抑制鼻咽癌的发生和转移而发挥其肿瘤抑制作用。进一步研究表明，NKILA通过核因子-kappaB途径调控鼻咽癌的转移。我们的研究表明，NKILA在鼻咽癌的发生发展中起着关键作用。这些发现特别重要，因为它们为炎症对鼻咽癌生物学的影响提供了新的见解。NKILA可能是鼻咽癌的候选分子标志物和新的治疗靶点。
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-kappa B 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-kappa B is a pivotal link between NPC and inflammation. Importantly, NF-kappa B 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-kappa B 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-kappa B 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.