PMID- 27638632 OWN - NLM STAT- MEDLINE DCOM- 20170531 LR - 20181113 IS - 1438-7948 (Electronic) IS - 1438-793X (Linking) VI - 17 IP - 2-3 DP - 2017 May TI - Regulatory network analysis of microRNAs and genes in imatinib-resistant chronic myeloid leukemia. PG - 263-277 LID - 10.1007/s10142-016-0520-1 [doi] AB - 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. FAU - Soltani, Ismael AU - Soltani I AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. soltaniismael@yahoo.fr. FAU - Gharbi, Hanen AU - Gharbi H AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Hassine, Islem Ben AU - Hassine IB AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Bouguerra, Ghada AU - Bouguerra G AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Douzi, Kais AU - Douzi K AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Teber, Mouheb AU - Teber M AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Abbes, Salem AU - Abbes S AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. FAU - Menif, Samia AU - Menif S AD - Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, Universite Tunis El Manar, Tunis, Tunisia. LA - eng PT - Journal Article DEP - 20160916 PL - Germany TA - Funct Integr Genomics JT - Functional & integrative genomics JID - 100939343 RN - 0 (MicroRNAs) RN - 8A1O1M485B (Imatinib Mesylate) SB - IM MH - Humans MH - Imatinib Mesylate/*therapeutic use MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy MH - MicroRNAs/*genetics OTO - NOTNLM OT - Chronic myeloid leukemia OT - Imatinib mesylate OT - MicroRNA OT - Network OT - Resistance OT - Transcription factor EDAT- 2016/09/18 06:00 MHDA- 2017/06/01 06:00 CRDT- 2016/09/18 06:00 PHST- 2016/04/29 00:00 [received] PHST- 2016/08/30 00:00 [accepted] PHST- 2016/08/20 00:00 [revised] PHST- 2016/09/18 06:00 [pubmed] PHST- 2017/06/01 06:00 [medline] PHST- 2016/09/18 06:00 [entrez] AID - 10.1007/s10142-016-0520-1 [pii] AID - 10.1007/s10142-016-0520-1 [doi] PST - ppublish SO - Funct Integr Genomics. 2017 May;17(2-3):263-277. doi: 10.1007/s10142-016-0520-1. Epub 2016 Sep 16.