胃肠病学
胃腸病學
위장병학
CHINESE JOURNAL OF GASTROENTEROLOGY
2015年
5期
267-271
,共5页
肖坤庭%史冬涛%虞竹雯%田文妍%陈卫昌
肖坤庭%史鼕濤%虞竹雯%田文妍%陳衛昌
초곤정%사동도%우죽문%전문연%진위창
胃肿瘤%基因,SEMA3B%基因,肿瘤抑制%DNA甲基化%基因表达调控
胃腫瘤%基因,SEMA3B%基因,腫瘤抑製%DNA甲基化%基因錶達調控
위종류%기인,SEMA3B%기인,종류억제%DNA갑기화%기인표체조공
Stomach Neoplasms%Genes,SEMA3B%Genes,Tumor Suppressor%DNA Methylation%Gene Expression Regulation
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 為一候選腫瘤抑製基因，在多種噁性腫瘤的髮生、髮展中起重要作用。目的：初步探討DNA 甲基化調控機製對胃癌中SEMA3B 基因錶達的影響。方法：以real-time PCR 檢測6株人胃癌細胞株（SGC7901、AGS、MGC803、BGC823、MKN45、HGC27）、正常人胃黏膜上皮細胞株GES-1和41例胃癌組織及其相應癌徬非癌組織中的SEMA3B mRNA 錶達。以甲基化特異性PCR 檢測SEMA3B 基因啟動子區甲基化狀態，併分析其與胃癌臨床病理特徵的關繫。以去甲基化藥物5-Aza-dC（10μmol/ L）處理上述細胞株72 h，觀察SEMA3B 基因甲基化狀態和mRNA 錶達變化。結果：6株胃癌細胞和胃癌組織中的SEMA3B mRNA 錶達分彆顯著低于GES-1細胞（ P <0.001）和相應癌徬非癌組織（P <0.01）。6株胃癌細胞SEMA3B 基因啟動子區均髮生甲基化，GES-1細胞則未髮生甲基化。胃癌組織SEMA3B 基因甲基化率顯著高于相應癌徬非癌組織（67.6%對32.4%，P <0.01），甲基化狀態與胃癌分化程度和淋巴結轉移相關（P <0.05）。經5-Aza-dC 處理後，5株胃癌細胞SEMA3B 基因甲基化程度下降，伴mRNA 錶達上調。結論：SEMA3B 基因啟動子區高甲基化可能是其在胃癌中錶達下調的原因之一，併參與瞭胃癌的髮生、髮展。SEMA3B 有望成為胃癌診斷和預後評估的分子標記物以及錶觀遺傳學治療靶點。
SEMA3B 위일후선종류억제기인，재다충악성종류적발생、발전중기중요작용。목적：초보탐토DNA 갑기화조공궤제대위암중SEMA3B 기인표체적영향。방법：이real-time PCR 검측6주인위암세포주（SGC7901、AGS、MGC803、BGC823、MKN45、HGC27）、정상인위점막상피세포주GES-1화41례위암조직급기상응암방비암조직중적SEMA3B mRNA 표체。이갑기화특이성PCR 검측SEMA3B 기인계동자구갑기화상태，병분석기여위암림상병리특정적관계。이거갑기화약물5-Aza-dC（10μmol/ L）처리상술세포주72 h，관찰SEMA3B 기인갑기화상태화mRNA 표체변화。결과：6주위암세포화위암조직중적SEMA3B mRNA 표체분별현저저우GES-1세포（ P <0.001）화상응암방비암조직（P <0.01）。6주위암세포SEMA3B 기인계동자구균발생갑기화，GES-1세포칙미발생갑기화。위암조직SEMA3B 기인갑기화솔현저고우상응암방비암조직（67.6%대32.4%，P <0.01），갑기화상태여위암분화정도화림파결전이상관（P <0.05）。경5-Aza-dC 처리후，5주위암세포SEMA3B 기인갑기화정도하강，반mRNA 표체상조。결론：SEMA3B 기인계동자구고갑기화가능시기재위암중표체하조적원인지일，병삼여료위암적발생、발전。SEMA3B 유망성위위암진단화예후평고적분자표기물이급표관유전학치료파점。
Background: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(10μmol/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 a promising epigenetic therapeutic target.
