5-Aza-2′-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene
5-Aza-2′-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating β-galactoside:α2,3-sialyltransferase 6 gene
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DOI：
10.1016/j.biocel.2010.12.015
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发表时间：
2011-04-01
影响因子：
4
通讯作者：
Cheng, Pi-Wan
中科院分区：
文献类型：
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作者：
Chachadi, Vishwanath B.;Cheng, Helen;Cheng, Pi-Wan
唾液酸刘易斯X是一种常见于晚期肿瘤的肿瘤相关抗原。然而，这种癌抗原的产生机制并不完全清楚。本研究的目的是检查表观遗传学是否参与这种抗原形成的调节。我们观察到用5-氮杂-2 '-脱氧胞苷处理的结肠癌细胞系HCT 15细胞中唾液酸刘易斯X增加。这种处理增强了MUD上β-半乳糖苷：α 2，3-唾液酸转移酶6基因和唾液酸刘易斯X的表达，以及这些细胞在动态流动条件下对E-选择素的粘附。此外，5-氮杂-2 '-脱氧胞苷处理抑制了β-半乳糖苷：α 2，3-唾液酸转移酶6基因的甲基化，并且该基因的siRNA敲低显著降低了唾液酸刘易斯X而不影响MUC 1表达。我们的结论是，5-氮杂-2 '-脱氧胞苷处理通过抑制DNA甲基化来刺激β-半乳糖苷：α 2，3-唾液酸转移酶6基因，从而增加MUC 1上的唾液酸刘易斯X。5-氮杂-2 '-脱氧胞苷增加唾液酸刘易斯X引起了对该化疗药物安全性的担忧。此外，β-半乳糖苷：α 2，3-唾液酸转移酶6基因可能是抑制结肠癌致瘤性的潜在治疗靶点。(C)2010爱思唯尔有限公司保留所有权利。
Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced cancers. However, the mechanism for the production of this cancer antigen is not entirely clear. The objective of this study is to examine whether epigenetics is involved in the regulation of the formation of this antigen. We observed an increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with 5-Aza-2'-deoxycytidine. This treatment enhanced the expression of beta-galactoside:alpha 2,3-sialyltransferase 6 gene and sialyl Lewis X on MUD, and the adherence of these cells to E-selectin under dynamic flow conditions. In addition, 5-Aza-2'-deoxycytidine treatment inhibited methylation of beta-galactoside:alpha 2,3-sialyltransferase 6 gene and siRNA knockdown of this gene drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude that 5-Aza-2'-deoxycytidine treatment increases sialyl Lewis X on MUC1 by stimulating the beta-galactoside:alpha 2,3-sialyltransferase 6 gene via inhibition of DNA methylation. Increased sialyl Lewis X by 5-Aza-2'-deoxycytidine raises a concern about the safety of this chemotherapeutic drug. In addition, beta-galactoside:alpha 2,3-sialyltransferase 6 gene may be a potential therapeutic target for suppressing tumorigenicity of colon cancer. (C) 2010 Elsevier Ltd. All rights reserved.