• Open Access

Down-regulated miR-331–5p and miR-27a are associated with chemotherapy resistance and relapse in leukaemia

Authors

  • Dan-Dan Feng,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Hua Zhang,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Peng Zhang,

    1. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
    Search for more papers by this author
  • Yu-Sheng Zheng,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Xing-Ju Zhang,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Bo-Wei Han,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Xue-Qun Luo,

    1. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Ling Xu,

    1. The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Hui Zhou,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Liang-Hu Qu,

    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Search for more papers by this author
  • Yue-Qin Chen

    Corresponding author
    1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
      Y. Q. CHEN, Key Laboratory of Gene Engineering of the Ministry of Education, Biotechnology Research Center, Sun Yat-sen University, Guangzhou 510275, China.
      Tel.: 86-20-84112739
      Fax: 86-20-84036551
      E-mail: lsscyq@mail.sysu.edu.cn
    Search for more papers by this author

Y. Q. CHEN, Key Laboratory of Gene Engineering of the Ministry of Education, Biotechnology Research Center, Sun Yat-sen University, Guangzhou 510275, China.
Tel.: 86-20-84112739
Fax: 86-20-84036551
E-mail: lsscyq@mail.sysu.edu.cn

Abstract

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.

Ancillary