TSPAN8作为一种预后标志物，参与鼻咽癌中的Akt/丝裂原活化蛋白激酶（MAPK）信号通路。
TSPAN8 serves as a prognostic marker involving Akt/MAPK pathway in nasopharyngeal carcinoma.
作者信息
Lin Xiao, Bi Zhuofei, Hu Qian, Li Qingjian, Liu Jieqiong, Luo Man-Li, Xiang Yanqun, Yao Herui
机构信息
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
出版信息
Ann Transl Med. 2019 Sep;7(18):470. doi: 10.21037/atm.2019.08.02.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common epithelial carcinoma with high occurrence and metastatic rates in Southern China. To date, the molecular mechanisms of metastasis for NPC remains unclear. The aim of this study was to discover the underlying mechanism of NPC and to elucidate novel genes that may play important roles in NPC progression and metastasis.
METHODS
We carry out mRNA expression profiling, Arraystar Human mRNA Expression Profiling Service Report based on polymerase chain reaction (PCR) using four pairs of tumor tissues and their corresponding benign adjacent tissues from NPC patients.
RESULTS
We found that 1,787 genes were differentially expressed, among them, 8 genes were identified as highly upregulated in NPC patients. Within these 8 genes, only TSPAN8 was consistently over-expressed in poorly differentiated CNE2 cell line and highly-metastatic subclone S18 cell line. TSPAN8 mRNA and protein levels were increased in primary carcinoma tissues compared to their corresponding adjacent benign tissues. Knockdown of TSPAN8 by siRNA resulted in inhibition of NPC cell migration and invasion, while overexpression of TSPAN8 promoted NPC cell migration, invasion and proliferation. To explore the potential metastasis pathway mechanism for NPC, TSPAN8 were silenced in CNE2 cell. From the Tumor Metastasis Pathway Finder PCR array, knockdown of TSPAN8 led to the down-regulation of IL-1β, which showed the most down-regulation among identified genes. IL-1β is a regulating factor of the Akt/MAPK pathway, which is involved in the cancer cell migration regulation. Furthermore, the down-regulation of TSPAN8 in CNE2 cell was associated with inhibition of the Akt/MAPK pathway. Immunohistochemistry (IHC) indicated that TSPAN8 level was increased in NPC tumors, which was associated with shorter overall survival and metastasis free survival (MFS).
CONCLUSIONS
The data indicated that TSPAN8 acting as a tumor migration marker and may be a prognostic factor or therapeutic target for NPC.
背景
鼻咽癌（NPC）是一种常见的上皮性癌，在中国南方发病率和转移率较高。迄今为止，鼻咽癌转移的分子机制仍不清楚。本研究的目的是发现鼻咽癌的潜在机制，并阐明可能在鼻咽癌进展和转移中起重要作用的新基因。
方法
我们使用来自鼻咽癌患者的四对肿瘤组织及其相应的良性相邻组织，基于聚合酶链反应（PCR）开展mRNA表达谱分析，即Arraystar人类mRNA表达谱分析服务报告。
结果
我们发现1787个基因存在差异表达，其中8个基因在鼻咽癌患者中被鉴定为高度上调。在这8个基因中，只有四跨膜蛋白8（TSPAN8）在低分化CNE2细胞系和高转移亚克隆S18细胞系中持续过度表达。与相应的相邻良性组织相比，原发性癌组织中TSPAN8 mRNA和蛋白水平升高。用小干扰RNA（siRNA）敲低TSPAN8导致鼻咽癌细胞迁移和侵袭受到抑制，而TSPAN8的过表达促进了鼻咽癌细胞的迁移、侵袭和增殖。为了探索鼻咽癌潜在的转移途径机制，在CNE2细胞中沉默TSPAN8。从肿瘤转移途径发现者PCR阵列中可知，敲低TSPAN8导致白细胞介素-1β（IL-1β）下调，在已鉴定的基因中其下调最为明显。IL-1β是Akt/丝裂原活化蛋白激酶（MAPK）途径的调节因子，参与癌细胞迁移调节。此外，CNE2细胞中TSPAN8的下调与Akt/MAPK途径的抑制有关。免疫组织化学（IHC）表明，鼻咽癌肿瘤中TSPAN8水平升高，这与较短的总生存期和无转移生存期（MFS）相关。
结论
数据表明，TSPAN8作为一种肿瘤迁移标志物，可能是鼻咽癌的一个预后因素或治疗靶点。
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