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Functional & Integrative Genomics

, Volume 17, Issue 2–3, pp 263–277 | Cite as

Regulatory network analysis of microRNAs and genes in imatinib-resistant chronic myeloid leukemia

  • Ismael Soltani
  • Hanen Gharbi
  • Islem Ben Hassine
  • Ghada Bouguerra
  • Kais Douzi
  • Mouheb Teber
  • Salem Abbes
  • Samia Menif
Original Article

Abstract

Targeted therapy in the form of selective breakpoint cluster region-abelson (BCR/ABL) tyrosine kinase inhibitor (imatinib mesylate) has successfully been introduced in the treatment of the chronic myeloid leukemia (CML). However, acquired resistance against imatinib mesylate (IM) has been reported in nearly half of patients and has been recognized as major issue in clinical practice. Multiple resistance genes and microRNAs (miRNAs) are thought to be involved in the IM resistance process. These resistance genes and miRNAs tend to interact with each other through a regulatory network. Therefore, it is crucial to study the impact of these interactions in the IM resistance process. The present study focused on miRNA and gene network analysis in order to elucidate the role of interacting elements and to understand their functional contribution in therapeutic failure. Unlike previous studies which were centered only on genes or miRNAs, the prime focus of the present study was on relationships. To this end, three regulatory networks including differentially expressed, related, and global networks were constructed and analyzed in search of similarities and differences. Regulatory associations between miRNAs and their target genes, transcription factors and miRNAs, as well as miRNAs and their host genes were also macroscopically investigated. Certain key pathways in the three networks, especially in the differentially expressed network, were featured. The differentially expressed network emerged as a fault map of IM-resistant CML. Theoretically, the IM resistance process could be prevented by correcting the included errors. The present network-based approach to study resistance miRNAs and genes might help in understanding the molecular mechanisms of IM resistance in CML as well as in the improvement of CML therapy.

Keywords

Chronic myeloid leukemia Imatinib mesylate Resistance MicroRNA Network Transcription factor 

Abbreviations

miRNA

MicroRNA

TFs

Transcription factors

IM

Imatinib mesylate

CML

Chronic myeloid leukemia

NCBI

National Center for Biotechnology Information

TFBSs

Transcription factor binding sites

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ismael Soltani
    • 1
  • Hanen Gharbi
    • 1
  • Islem Ben Hassine
    • 1
  • Ghada Bouguerra
    • 1
  • Kais Douzi
    • 1
  • Mouheb Teber
    • 1
  • Salem Abbes
    • 1
  • Samia Menif
    • 1
  1. 1.Molecular and Cellular Hematology Laboratory, Institut Pasteur de TunisUniversité Tunis El ManarTunisTunisia

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