miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221
miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221
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DOI：
10.1182/blood-2008-12-191619
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发表时间：
2009-11-05
期刊：
影响因子：
20.3
通讯作者：
Lodish, Harvey F.
中科院分区：
文献类型：
--
作者：
Kotani, Ai;Ha, Daon;Lodish, Harvey F.
MLL-AF4 急性淋巴细胞白血病 (ALL) 预后较差。 MicroRNA (miRNA) 是一种小型非编码 RNA，可在转录后调节靶 mRNA 的表达。我们对之前发表的数据的分析表明，相对于其他类型的 ALL，MLL 重排 ALL 中 miR-128b 和 miR-221 的表达下调。这些 miRNA 的重新表达共同使 2 个培养的 MLL-AF4 ALL 细胞系对糖皮质激素敏感。 miR-128b下调的靶基因包括MLL、AF4以及MLL-AF4和AF4-MLL融合基因； miR-221 下调 CDKN1B。这些结果表明，miR-128b 和 miR-221 的下调与糖皮质激素耐药有关，并且恢复其水平是 MLL-AF4 ALL 的潜在治疗方法。 （血。2009；114：4169-4178）
MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL. (Blood. 2009; 114:4169-4178)