Saito Yoshimasa, Liang Gangning, Egger Gerda, Friedman Jeffrey M, Chuang Jody C, Coetzee Gerhard A, Jones Peter A
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA.
Cancer Cell. 2006 Jun;9(6):435-43. doi: 10.1016/j.ccr.2006.04.020.
Expression profiling of T24 cells revealed that 17 out of 313 human miRNAs were upregulated more than 3-fold by simultaneous treatment with the chromatin-modifying drugs 5-aza-2'-deoxycytidine and 4-phenylbutyric acid. One of these, miR-127, is embedded in a CpG island and is highly induced from its own promoter after treatment. miR-127 is usually expressed as part of a miRNA cluster in normal cells but not in cancer cells, suggesting that it is subject to epigenetic silencing. In addition, the proto-oncogene BCL6, a potential target of miR-127, was translationally downregulated after treatment. These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors.
T24细胞的表达谱分析显示，在313个人类miRNA中，有17个在同时用染色质修饰药物5-氮杂-2'-脱氧胞苷和4-苯丁酸处理后上调超过3倍。其中之一miR-127，位于一个CpG岛中，处理后从其自身启动子高度诱导表达。miR-127在正常细胞中通常作为miRNA簇的一部分表达，但在癌细胞中不表达，这表明它受到表观遗传沉默的影响。此外，原癌基因BCL6是miR-127的潜在靶标，处理后其翻译水平下调。这些结果表明，DNA去甲基化和组蛋白脱乙酰酶抑制可激活可能作为肿瘤抑制因子的miRNA的表达。
