miR-145-5p and miR-203a-5p overcome imatinib resistance in myelogenous leukemic cells through metabolic reprogramming

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dc.contributor.authorSingh, Priyanka
dc.contributor.authorGupta, Sonu Kumar
dc.contributor.authorAli, Villayat
dc.contributor.authorChhabra, Ravindresh
dc.contributor.authorVerma, Malkhey
dc.date.accessioned2024-01-16T14:23:22Z
dc.date.accessioned2024-08-13T10:34:16Z
dc.date.available2024-01-16T14:23:22Z
dc.date.available2024-08-13T10:34:16Z
dc.date.issued2023-03-01T00:00:00
dc.description.abstractImatinib is the most effective therapy for chronic myeloid leukemia (CML), but many patients eventually develop resistance to it after an initial satisfactory response. This study investigated the potential of three miRNAs (miR-106b-5p, miR-145-5p, miR-203a-5p) in overcoming imatinib resistance in leukemic cells. The imatinib-resistant K562 (IR-K562) cells were developed and transfected with one of the three miRNAs to evaluate their potency in overcoming imatinib resistance. The changes in the metabolic profile were studied using flux balance analysis (FBA) and the data was validated using qRT-PCR.Among the three miRNAs, the ectopic expression of either miR-145-5p or miR-203a-5p was able to sensitize the IR-K562 cells to imatinib. The concentration of key oncometabolites; glucose, lactate, and glutamine, in the culture media of the miR-transfected IR-K562 cells, reverted to the same levels as seen in imatinib-sensitive K562 cells. In addition, the FBA analysis revealed that the metabolism of lipid, fatty acids, and electron transport chain were significantly altered in resistant cells. The FBA data was also validated at the molecular level. Interestingly, the imatinib treatment coupled with the transfection of miR-145-5p or miR-203a-5p cells could reverse the metabolic flux of IR-K562 to the levels seen in imatinib-sensitive K562 cells. This study highlights the key metabolic changes that occur during development of imatinib resistance. It also identifies the specific miRNAs which can be targeted to overcome imatinib resistance in CML. � 2023, National Institute of Science Communication and Policy Research. All rights reserved.en_US
dc.identifier.doi10.56042/IJBB.V60I3.66526
dc.identifier.issn3011208
dc.identifier.urihttps://doi.org/10.56042/IJBB.V60I3.66526
dc.identifier.urihttp://10.2.3.109/handle/32116/2919
dc.language.isoen_USen_US
dc.publisherNational Institute of Science Communication and Policy Researchen_US
dc.subjectChemoresistanceen_US
dc.subjectFlux balance analysis (FBA)en_US
dc.subjectK562en_US
dc.subjectmiRNAsen_US
dc.subjectOncometabolitesen_US
dc.titlemiR-145-5p and miR-203a-5p overcome imatinib resistance in myelogenous leukemic cells through metabolic reprogrammingen_US
dc.title.journalIndian Journal of Biochemistry and Biophysicsen_US
dc.typeArticleen_US
dc.type.accesstypeOpen Accessen_US

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