胃癌中SEMA3B基因表达与其启动子区甲基化的关系  

Relationship between SEMA3B Gene Expression and its Promoter Methylation in Gastric Cancer

作　　者：肖坤庭 史冬涛[1] 虞竹雯 田文妍[1] 陈卫昌[1] 

机构地区：[1]苏州大学附属第一医院消化内科,215006

出　　处：《胃肠病学》2015年第5期267-271,共5页Chinese Journal of Gastroenterology

基　　金：江苏省高校自然科学研究面上项目(14KJB320014)

摘　　要：背景:SEMA3B为一候选肿瘤抑制基因,在多种恶性肿瘤的发生、发展中起重要作用。目的:初步探讨DNA甲基化调控机制对胃癌中SEMA3B基因表达的影响。方法:以real-time PCR检测6株人胃癌细胞株(SGC7901、AGS、MGC803、BGC823、MKN45、HGC27)、正常人胃黏膜上皮细胞株GES-1和41例胃癌组织及其相应癌旁非癌组织中的SEMA3B mRNA表达。以甲基化特异性PCR检测SEMA3B基因启动子区甲基化状态,并分析其与胃癌临床病理特征的关系。以去甲基化药物5-Aza-dC(10μmol/L)处理上述细胞株72 h,观察SEMA3B基因甲基化状态和mRNA表达变化。结果:6株胃癌细胞和胃癌组织中的SEMA3B mRNA表达分别显著低于GES-1细胞(P<0.001)和相应癌旁非癌组织(P<0.01)。6株胃癌细胞SEMA3B基因启动子区均发生甲基化,GES-1细胞则未发生甲基化。胃癌组织SEMA3B基因甲基化率显著高于相应癌旁非癌组织(67.6%对32.4%,P<0.01),甲基化状态与胃癌分化程度和淋巴结转移相关(P<0.05)。经5-Aza-dC处理后,5株胃癌细胞SEMA3B基因甲基化程度下降,伴mRNA表达上调。结论:SEMA3B基因启动子区高甲基化可能是其在胃癌中表达下调的原因之一,并参与了胃癌的发生、发展。SEMA3B有望成为胃癌诊断和预后评估的分子标记物以及表观遗传学治疗靶点。SEMA3B is a candidate tumor suppressor gene, which plays an essential role in tumorigenesis and progression of a wide variety of cancer. Aims： To explore preliminarily the influence of DNA methylation on regulation of SEMA3B gene expression in gastric cancer. Methods： Real-time PCR was used to determine the expression of SEMA3B mRNA in six human gastric cancer cell lines （SGC7901, AGS, MGC803, BGC823, MKN45, and HGC27）, one gastric epithelial cell line （ GES-1 ）, and 41 gastric cancer tissue and paired adjacent noncancerous tissue specimens. Methylation specific PCR was used to detect the promoter methylation of SEMA3B gene, and correlation between methylation of SEMA3B gene and clinicopathological characteristics of gastric cancer was analyzed. After treated with a demethylation agent, 5-Aza-dC （ 10 ~Lmol/L）, for 72 hours, the methylation and mRNA expression of SEMA3B gene were re-examined in above-mentioned cell lines. Results： SEMA3B mRNA expression was significantly lower in six gastric cancer cell lines and gastric cancer tissues than that in GES-1 cells （ P 〈 0. 001 ） and paired adjacent noncancerous tissues （ P 〈 0. 01 ）. Promoter methylation of SEMA3B gene could be detected in all six gastric cancer cell lines but not GES-1 cells. Frequency of SEMA3B gene methylation was significantly higher in gastric cancer tissues than in paired adjacent noncancerous tissues （67.6% vs. 32.4%, P 〈 0.01 ）, and the frequency was correlated with differentiation and lymph node metastasis of gastric cancer （P 〈 0.05）. After treated with 5-Aza-dC, hypermethylation of SEMA3B gene in 5 gastric cancer cell lines was decreased, accompanied by up-regulation of SEMA3B mRNA expression. Conclusions： Hypermethylation in promoter of SEMA3B gene might be one of the mechanisms accounting for the reduced expression of SEMA3B, and being involved in tumorigenesis and progression of gastric cancer. SEMA3B might be a potential biomarker for diagnosis and prognostic assessment for gastric cancer and

关 键 词：胃肿瘤 基因 SEMA3B 基因 肿瘤抑制 DNA甲基化 基因表达调控 

分 类 号：R735.2[医药卫生—肿瘤]