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LncRNA MEG3 Regulates Imatinib Resistance in Chronic Myeloid Leukemia via Suppressing MicroRNA-21  

Zhou, Xiangyu (Department of Vascular and Thyroid, the Affiliated Hospital of Southwest Medical University)
Yuan, Ping (Department of Neurology, the Affiliated Hospital of Southwest Medical University)
Liu, Qi (Department of Pediatrics, Nanchong Central Hospital)
Liu, Zhiqiang (Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center)
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Biomolecules & Therapeutics / v.25, no.5, 2017 , pp. 490-496 More about this Journal
Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.
Chronic myeloid leukemia; Imatinib; Drug resistance; MEG3; MiR-21;
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