microRNA-125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis

被引:28
|
作者
Zhou, Lili [1 ]
Bai, Haitao [1 ]
Wang, Chun [1 ]
Wei, Daolin [1 ]
Qin, Youwen [1 ]
Xu, Xiaowei [1 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Hematol, Affiliated Shanghai Peoples Hosp 1, Shanghai 200080, Peoples R China
关键词
microRNA-125b; GRK2; PUMA; daunorubicin; acute leukemia; ACUTE MYELOID-LEUKEMIA; ANTAGONIST KILLER 1; DRUG-RESISTANCE; UP-REGULATION; CANCER-CELLS; MIR-125B; EXPRESSION; TUMOR; CONFERS; SURVIVAL;
D O I
10.3892/mmr.2014.2011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP-1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.
引用
收藏
页码:1909 / 1916
页数:8
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