微小RNA-128b是MLL-AF4急性淋巴细胞白血病细胞中的一种强效糖皮质激素敏化剂，并与微小RNA-221发挥协同作用。
miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.
作者信息
Kotani Ai, Ha Daon, Hsieh James, Rao Prakash K, Schotte Diana, den Boer Monique L, Armstrong Scott A, Lodish Harvey F
机构信息
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
出版信息
Blood. 2009 Nov 5;114(19):4169-78. doi: 10.1182/blood-2008-12-191619. Epub 2009 Sep 11.
Abstract
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.
摘要
MLL-AF4急性淋巴细胞白血病（ALL）预后较差。微小RNA（miRNA）是一类小的非编码RNA，可在转录后调节靶mRNA的表达。我们对先前发表数据的分析表明，相对于其他类型的ALL，miR-128b和miR-221在MLL重排的ALL中表达下调。这些miRNA的重新表达协同使2株MLL-AF4 ALL细胞培养系对糖皮质激素敏感。被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，恢复其水平可能是MLL-AF4 ALL中一种有前景的治疗方法。
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