Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562
Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562
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DOI：
10.1016/j.bbrc.2012.07.098
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发表时间：
2012-08-24
影响因子：
3.1
通讯作者：
Liang, Yingmin
中科院分区：
文献类型：
--
作者：
Liu, Li;Wang, Sitao;Liang, Yingmin
伊马替尼耐药仍然是CML治疗的一大障碍。以往的研究表明c-myc在bcr-abl CML细胞增殖中起重要作用，但其在伊马替尼耐药中的作用尚不清楚。在这项研究中，我们首次发现c-myc表达在伊马替尼耐药的K562 R细胞中上调，这反过来又增强了miR-144/451的表达。K562 R细胞中c-myc的敲低或miR-144/451的恢复使K562 R细胞对伊马替尼治疗敏感。我们的研究揭示了myc和miR-144/451之间的调节途径，并强调靶向myc或miR-144/451可能对于消除伊马替尼耐药CML细胞有价值。(c)2012 Elsevier Inc. All rights reserved.
Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells. (c) 2012 Elsevier Inc. All rights reserved.