MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.
MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.
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DOI：
10.1038/leu.2014.276
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发表时间：
2015-04
期刊：
影响因子：
11.4
通讯作者：
Speleman F
中科院分区：
文献类型：
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作者：
Mets E;Van der Meulen J;Van Peer G;Boice M;Mestdagh P;Van de Walle I;Lammens T;Goossens S;De Moerloose B;Benoit Y;Van Roy N;Clappier E;Poppe B;Vandesompele J;Wendel HG;Taghon T;Rondou P;Soulier J;Van Vlierberghe P;Speleman F
MYB癌基因是正常和恶性造血所必需的亮氨酸拉链转录因子。在T细胞急性淋巴细胞白血病（T-ALL）中，升高的MYB水平可直接通过T细胞受体介导的MYB易位、基因组MYB复制或MYB基因座处的TAL 1复合物结合增强或间接通过TAL 1/miR-223/FBXW 7调节轴产生。在这项研究中，我们使用了一个公正的MYB 3′非翻译区microRNA（miRNA）文库筛选，并确定了33个推定的MYB靶向miRNA。随后，使用来自两个独立的T-ALL群组和正常T细胞的不同子集的转录组数据来选择在正常和恶性T细胞转化的背景下具有相关性的miRNA。因此，miR-193 b-3 p被鉴定为在恶性T细胞转化期间靶向MYB的新型真正的肿瘤抑制miRNA，从而为针对人T-ALL的有效MYB靶向导向疗法提供切入点。
The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3′untranslated region–microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.