Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365
Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365
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源自伊马替尼耐药慢性粒细胞白血病细胞的外泌体通过传递 miR-365 介导耐药性状的水平转移
DOI：
10.1016/j.yexcr.2017.12.001
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发表时间：
2018-01-15
影响因子：
3.7
通讯作者：
Huang, Bo
中科院分区：
文献类型：
--
作者：
Min, Qing-Hua;Wang, Xiao-Zhong;Huang, Bo
慢性粒细胞白血病（CML）是造血干/祖细胞的恶性疾病。大多数患者可以使用酪氨酸激酶抑制剂（TKI）（如伊马替尼）进行有效治疗，但部分患者会产生耐药性。越来越多的证据表明，癌症中的外泌体是肿瘤进展的促进剂。在此，我们发现来自伊马替尼耐药CML细胞的外泌体可以内化到敏感CML细胞中并赋予耐药性特征。我们还使用微阵列和qRT-PCR证明了与来自敏感细胞的外泌体相比，来自耐药CML细胞的外泌体中miR-365的水平显著更高。与对照组相比，转染pre-miR-365的伊马替尼敏感CML细胞显示出较低的化疗敏感性和凋亡率。我们进一步证实了miR 365的外泌体转移通过抑制敏感CML细胞中促凋亡蛋白的表达而诱导耐药性。总之，我们的研究揭示了外泌体通过递送miR-365介导慢性髓细胞白血病细胞中耐药性状的水平转移。
Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR. The imatinib sensitive CML cells transfected with pre-miR-365 displayed lower chemosensitivity and apoptosis rate compared with controls. We further confirmed that exosomal transfer of miR365 induced drug resistance by inhibiting expression of pro-apoptosis protein in sensitive CML cells. In conclusion, our study reveals that exosomes mediate a horizontal transfer of drug-resistant trait in chronic myeloid leukemia cell by delivering miR-365.