Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.
Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.
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整合素α9基因启动子在鼻咽癌中高甲基化和下调
DOI：
10.18632/oncotarget.5154
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Ernberg I
中科院分区：
文献类型：
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作者：
Nawaz I;Hu LF;Du ZM;Moumad K;Ignatyev I;Pavlova TV;Kashuba V;Almgren M;Zabarovsky ER;Ernberg I
启动子甲基化导致的肿瘤抑制基因（TSG）的表观遗传沉默可能是多步骤致癌过程中的早期事件。人类 3 号染色体含有与多种癌症类型相关的 TSG 簇，包括中国南方最常见的癌症——鼻咽癌 (NPC)。在使用 NotI 微阵列在 3 号染色体上鉴定的 10 个候选 TSG 中，ITGA9 和 WNT7A 可以得到验证。 5'-aza-2'脱氧胞苷处理恢复了两种NPC细胞系中ITGA9和WNT7A的表达。免疫染色显示这些基因在邻近对照鼻咽上皮细胞的膜和细胞质中强表达，而在鼻咽癌肿瘤细胞中弱表达。 ITGA9启动子在肿瘤和对照组织之间显示出显着的差异甲基化，而WNT7A启动子没有检测到差异甲基化。与对照中的表达相比，鼻咽癌肿瘤中ITGA9的表达水平下调了4.9倍。通过甲基化特异性 PCR (MSP) 在 56% 的 EBV 阳性 NPC 病例中检测到 ITGA9 甲基化，特异性为 100%。综上所述，这表明 ITGA9 可能是 NPC 中参与肿瘤细胞生物学的 TSG。应进一步探讨使用 ITGA9 甲基化作为早期检测鼻咽癌标志物的可能性。
Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5′-aza-2′ deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC- cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored.