Down-regulated miR-331-5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia.
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.
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China.
Dan-Dan
DD
Feng
Hua
H
Zhang
Peng
P
Zhang
Yu-Sheng
YS
Zheng
Xing-Ju
XJ
Zhang
Bo-Wei
BW
Han
Xue-Qun
XQ
Luo
Ling
L
Xu
Hui
H
Zhou
Liang-Hu
LH
Qu
Yue-Qin
YQ
Chen
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D014176:Protein Biosynthesis; D012008:Recurrence
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; C531388:MIRN27 microRNA, human; C544460:MIRN331 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin