Upregulation of miR-99a is associated with poor prognosis of acute myeloid leukemia and promotes myeloid leukemia cell expansion.
Upregulation of miR-99a is associated with poor prognosis of acute myeloid leukemia and promotes myeloid leukemia cell expansion.
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miR-99a 的上调与急性髓系白血病的不良预后相关，并促进髓系白血病细胞的扩增。
DOI：
10.18632/oncotarget.12947
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发表时间：
2016-11-22
期刊：
影响因子：
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通讯作者：
Zhou Y
中科院分区：
文献类型：
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作者：
Si X;Zhang X;Hao X;Li Y;Chen Z;Ding Y;Shi H;Bai J;Gao Y;Cheng T;Yang FC;Zhou Y
白血病干细胞（LSC）可以抵抗导致疾病进展和/或复发的可用治疗。为了剖析急性髓性白血病（AML）复发的微小RNA（miRNA）表达特征，使用来自不同疾病阶段的AML患者的配对骨髓样品的富集的LSC进行miRNA阵列分析。我们发现，与初次诊断时收集的LSC相比，复发时获得的LSC中miR-99 a显著上调。我们还发现，在较大的AML患者队列中，与非LSC相比，LSC中的miR-99 a上调，并且miR-99 a的较高表达水平与这些AML患者的总体生存率和无事件生存率显著相关。miR-99 a的异位表达导致髓性白血病细胞在体外和体内暴露于化疗药物后的集落形成能力和扩增增加，部分原因是克服了化疗药物介导的细胞周期阻滞。基因分析和生物信息学分析表明，miR-99 a的异位表达显著上调了对LSC维持、细胞周期以及E2 F和MYC下游靶点至关重要的基因。这项研究表明，miR-99 a在髓系白血病进展中具有新的作用和作为生物标志物的潜在用途。
Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients. Ectopic expression of miR-99a led to increased colony forming ability and expansion in myeloid leukemia cells after exposure to chemotherapeutic drugs in vitro and in vivo, partially due to overcoming of chemotherapeutic agent-mediated cell cycle arrest. Gene profiling and bioinformatic analyses indicated that ectopic expression of miR-99a significantly upregulated genes that are critical for LSC maintenance, cell cycle, and downstream targets of E2F and MYC. This study suggests that miR-99a has a novel role and potential use as a biomarker in myeloid leukemia progression.
影响因子：
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作者：
Navakauskienė R;Borutinskaitė VV;Treigytė G;Savickienė J;Matuzevičius D;Navakauskas D;Magnusson KE
通讯作者：
Magnusson KE