Tumor suppressor DYRK1A effects on proliferation and chemoresistance of AML cells by downregulating c-Myc.
Tumor suppressor DYRK1A effects on proliferation and chemoresistance of AML cells by downregulating c-Myc.
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肿瘤抑制因子 DYRK1A 通过下调 c-Myc 影响 AML 细胞的增殖和化疗耐药性
DOI：
10.1371/journal.pone.0098853
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Liu Q;Liu N;Zang S;Liu H;Wang P;Ji C;Sun X
急性髓系白血病（acute myeloid leukemia，AML）是由造血祖细胞异常增殖和聚集引起的成人最常见的恶性肿瘤之一。我们在这里报告DYRK 1A的表达水平降低，在成人AML患者的骨髓，与正常对照组相比。过表达DYRK 1A可通过增加G 0/G1期细胞比例抑制AML细胞的增殖。我们推断增殖抑制是由于DYRK 1A通过介导其降解下调c-Myc。此外，c-Myc的过表达显著逆转了DYRK 1A诱导的AML细胞生长抑制。与初治AML患者相比，复发/难治AML患者中DYRK 1A的表达明显降低，提示DYRK 1A在AML化疗耐药中的作用。本研究为DYRK 1A在AML中作为潜在的抑癌基因提供了功能证据。
Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of c-Myc by DYRK1A, through mediating its degradation. Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition induced by DYRK1A. DYRK1A also had significantly lower expression in relapsed/refractory AML patients, comparing to newly-diagnosed AML patients, which indicated the role of DYRK1A in chemoresistance of AML. Our study provided functional evidences for DYRK1A as a potential tumor suppressor in AML.
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影响因子：
3.5
作者：
Altafaj, X;Dierssen, M;Estivill, X
通讯作者：
Estivill, X
影响因子：
50.3
作者：
Gregory MA;Phang TL;Neviani P;Alvarez-Calderon F;Eide CA;O'Hare T;Zaberezhnyy V;Williams RT;Druker BJ;Perrotti D;Degregori J
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作者：
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通讯作者：
Tejedor, Francisco J.