Let-7b regulates the adriamycin resistance of chronic myelogenous leukemia by targeting AURKB in K562/ADM cells
Let-7b regulates the adriamycin resistance of chronic myelogenous leukemia by targeting AURKB in K562/ADM cells
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Let-7b通过靶向K562/ADM细胞中的AURKB调节慢性粒细胞白血病的阿霉素耐药
DOI：
10.1080/10428194.2020.1811269
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Zhou X;Ma X;Sun H;Li X;Cao H;Jiang Y;Wang P;Xie S;Li Y;Sun Y
慢性髓系白血病（Chronic myeloid leukemia， CML）是一种恶性血液病，耐药往往与预后不良有关。MicroRNAs （miRNA）在转录调控、细胞发育和化疗耐药中起着关键作用。在这里，我们描述了let-7b对耐药白血病细胞的作用，并检查了let-7b作为阿霉素耐药生物标志物的相关性。结果表明，在K562/ADM （KA）细胞中，let-7b表达下调，K562和KA细胞中let-7b表达下调增加了对ADM的抗性。let-7b的抑制随后诱导AURKB的上调。最后，结果证明Pi3k/Akt/Erk通路与aurkb活化的耐药有关。我们的研究表明let-7b的过表达和AURKB的过表达参与了CML的耐药，其功能部分受Pi3k/Akt/Erk通路的调控。因此，我们对其抑制作用的进一步了解可能为克服CML化疗耐药提供新的治疗策略。
Abstract Chronic myeloid leukemia (CML) is a malignant hematological disease, and drug resistance is often related to poor prognosis. MicroRNAs (miRNA) play a pivotal role in transcriptional regulation, cell development, and chemotherapy resistance. Here, we describe the effect of let-7b on resistant leukemia cells and examine the relevance of let-7b as a biomarker for adriamycin resistance. Results showed that let-7b was downregulated in K562/ADM (KA) cells, and the downregulation of let-7b in K562 and KA cells increased ADM resistance. The inhibition of let-7b subsequently induced the upregulation of AURKB. Finally, results proved that the Pi3k/Akt/Erk pathway was related to AURKB-activated resistance. Our research indicated that the underexpression of let-7b and overexpression of AURKB contributed to the resistance of CML, and its function is partly regulated by the Pi3k/Akt/Erk pathway. Thus, our further understand of its inhibitory effect may promise a new therapeutic strategy to overcome chemotherapeutic resistance in CML.