Nebulin突变与甲状腺癌发生相关性的探究  

Unraveling the relationship between Nebulin mutation and thyroid carcinoma

作　　者：汪浩勇 李欣 聂霄月 方毅 胡勇 刘子敬 曹诚[2] WANG Haoyong;LI Xin;NIE Xiaoyue;FANG Yi;HU Yong;LIU Zijing;CAO Cheng(School of Food and Biological Engineering,Hubei University of Technology,Wuhan 430068,China;laboratory of Genetic Engineering,Beijing Institute of Biotechnology,Beijing 100850,China;department of Endocrinology,The Fifth Medical Center,Chinese PLA General Hospital,Beijing 100071,China)

机构地区：[1]湖北工业大学生物工程与食品学院,武汉430068 [2]北京生物工程研究所基因工程实验室,北京100850 [3]解放军总医院第五医学中心内分泌科,北京100071

出　　处：《生命的化学》2020年第7期1162-1170,共9页Chemistry of Life

基　　金：国家重点研究开发计划(2018YFC1200701)。

摘　　要：基因突变导致的基因功能异常是甲状腺癌发生的重要原因。在59例甲状腺癌患者中有20例患者的Nebulin(NEB)基因在V1696A位点发生了突变,突变比例显著高于正常人,这提示NEB突变与癌症的发生发展相关。因此,构建了NEB突变鼠来研究NEB突变对甲状腺的影响。利用高通量测序技术对野生型鼠和NEB突变鼠进行了转录组分析,选择差异基因通过实时荧光定量PCR(RT-qPCR)进行验证。在突变鼠中上调了217个基因以及下调了185个基因的表达。差异表达基因功能富集的通路及生物过程显示这些显著差异基因与甲状腺相关疾病、炎症、代谢途径和干扰素应答有关,并且在RT-qPCR结果中与癌症相关的基因表达差异显著,表明小鼠NEB突变与甲状腺癌的发生有关联,为后续功能性研究奠定了基础。Abnormal gene function owing to mutation is an important cause of thyroid cancer.V1696 A mutation in Nebulin gene(NEB)was at a significantly higher rate in 59 thyroid carcinoma patients than that in normal people,suggesting a link between NEB mutation and thyroid cancer.Therefore,we constructed NEB point mutant mouse line to study the effect of NEB mutation on the thyroid.Transcriptome analysis was performed on wild-type mice and NEB mutant mice using high-throughput sequencing technology.The differentially expressed genes(DEGs)were selected and verified with real-time quantitative PCR(RTqPCR).A total of 217 genes were up-regulated and 185 genes were down-regulated in mutant mice.Analysis of pathways and biological processes of DEG enrichment showed that these DEGs were mainly related to thyroid-related diseases,inflammation,metabolic pathways and interferon response.RT-qPCR results indicated that the expression level of some cancer-related genes was obviously changed in mutant mice,suggesting that NEB mutation in mice was associated with the occurrence of thyroid carcinoma.It laid the foundation for the subsequent functional research.

关 键 词：甲状腺癌 NEB 转录组测序 差异表达基因 

分 类 号：R736.1[医药卫生—肿瘤]