Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells
Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells
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DOI：
10.1016/j.ccr.2006.04.020
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发表时间：
2006-06-01
期刊：
影响因子：
50.3
通讯作者：
Jones, Peter A.
中科院分区：
文献类型：
--
作者：
Saito, Yoshimasa;Liang, Gangning;Jones, Peter A.
T24细胞的表达谱显示，通过染色质修饰药物5-aza-2'-脱氧胞苷和4-苯基丁酸同时处理，313个人类mirna中有17个上调了3倍以上。其中之一，miR-127，嵌入CpG岛中，并在处理后由其自身启动子高度诱导。miR-127通常在正常细胞中作为miRNA簇的一部分表达，而在癌细胞中不表达，这表明它受表观遗传沉默的影响。此外，原癌基因BCL6 （miR-127的潜在靶点）在治疗后被翻译下调。这些结果表明，DNA去甲基化和组蛋白去乙酰化酶抑制可以激活可能作为肿瘤抑制因子的mirna的表达。
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.