Open AccessDown‐regulated miR‐331–5p and miR‐27a are associated with chemotherapy resistance and relapse in leukaemia
Author(s) -
Feng DanDan,
Zhang Hua,
Zhang Peng,
Zheng YuSheng,
Zhang XingJu,
Han BoWei,
Luo XueQun,
Xu Ling,
Zhou Hui,
Qu LiangHu,
Chen YueQin
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01213.x
Subject(s) - microrna , cancer research , drug resistance , hl60 , k562 cells , cell culture , multiple drug resistance , p glycoprotein , transfection , chemotherapy , doxorubicin , biology , medicine , downregulation and upregulation , leukemia , oncology , immunology , gene , genetics
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.