Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.
Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.
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下调的miR-331-5p和miR-27a与白血病的化学疗法耐药性和复发有关。
DOI：
10.1111/j.1582-4934.2010.01213.x
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发表时间：
2011-10
影响因子：
5.3
通讯作者：
Chen YQ
中科院分区：
文献类型：
--
作者：
Feng DD;Zhang H;Zhang P;Zheng YS;Zhang XJ;Han BW;Luo XQ;Xu L;Zhou H;Qu LH;Chen YQ
多药耐药（MDR）和疾病复发是白血病治疗中具有挑战性的临床问题。复发性疾病通常是化疗难治性的，并表现出多重耐药性。因此，重要的是要确定癌细胞产生耐药性的机制。在这项研究中，我们使用microRNA（miRNA）微阵列和qRT-PCR方法，以调查的miRNAs表达在三个白血病细胞系与不同程度的耐阿霉素（DOX）相比，其亲本细胞系，K562。在耐药逐渐增加的白血病细胞系中，miR-331- 5 p和miR-27 a的表达与耐药因子P-糖蛋白（P-gp）的表达呈负相关。耐药性的发展受P-gp表达的调节。用miR-331- 5 p和miR-27 a单独或组合转染K562和人早幼粒细胞细胞系（HL）HL 60 D 0X抗性细胞，导致细胞对D 0X的敏感性增加，这表明改变的miRNA表达的校正可用于克服白血病细胞抗性的治疗策略。重要的是，与诊断时的原发患者相比，一组复发患者中miR-331- 5 p和miR-27 a的表达水平也较低，进一步说明白血病复发可能是miR-331- 5 p和miR-27 a失调的结果。
Multidrug resistance (MDR) and disease relapse are challenging clinical problems in the treatment of leukaemia. Relapsed disease is frequently refractory to chemotherapy and exhibits multiple drug resistance. Therefore, it is important to identify the mechanism by which cancer cells develop resistance. In this study, we used microRNA (miRNA) microarray and qRT-PCR approaches to investigate the expression of miRNAs in three leukaemia cell lines with different degrees of resistance to doxorubicin (DOX) compared with their parent cell line, K562. The expression of miR-331–5p and miR-27a was inversely correlated with the expression of a drug-resistant factor, P-glycoprotein (P-gp), in leukaemia cell lines with gradually increasing resistance. The development of drug resistance is regulated by the expression of the P-gp. Transfection of the K562 and, a human promyelocytic cell line (HL) HL60 DOX-resistant cells with miR-331–5p and miR-27a, separately or in combination, resulted in the increased sensitivity of cells to DOX, suggesting that correction of altered expression of miRNAs may be used for therapeutic strategies to overcome leukaemia cell resistance. Importantly, miR-331–5p and miR-27a were also expressed at lower levels in a panel of relapse patients compared with primary patients at diagnosis, further illustrating that leukaemia relapse might be a consequence of deregulation of miR-331–5p and miR-27a.
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影响因子：
6.4
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Abdelrahim, Maen;Abudayyeh, Ala;Jutooru, Indira;Chadalapaka, Gayathri;Wu, Fei;Mertens-Talcott, Susanne;Vanderlaag, Kathy;Cho, Sung Dae;Smith, Roger, III;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Mertens-Talcott, Susanne U.;Chintharlapalli, Sudhakar;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
20.3
作者：
Navarro, Alfons;Diaz, Tania;Monzo, Mariano
通讯作者：
Monzo, Mariano
影响因子：
8.4
作者：
Cho, William C. S.;Chow, Andrew S. C.;Au, Joseph S. K.
通讯作者：
Au, Joseph S. K.