Comparative expression analysis of dasatinib and ponatinib-regulated lncRNAs in chronic myeloid leukemia and their network analysis

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dc.authoridBiray Avcı, Cigir/0000-0001-8251-4520
dc.authoridAŞIK, Aycan/0000-0002-4123-4175
dc.authoridGunduz, Cumhur/0000-0002-6593-3237
dc.authorwosidBiray Avcı, Cigir/GWV-1665-2022
dc.authorwosidAŞIK, Aycan/A-8211-2019
dc.authorwosidGunduz, Cumhur/GOP-0629-2022
dc.contributor.authorKayabaşı, Çağla
dc.contributor.authorCaner, Ayşe
dc.contributor.authorYılmaz Susluer, Sunde
dc.contributor.authorBalcı Okcanoglu, Tuğce
dc.contributor.authorÖzmen Yelken, Besra
dc.contributor.authorAşık, Aycan
dc.contributor.authorMutlu, Zeynep
dc.date.accessioned2023-03-22T19:47:22Z
dc.date.available2023-03-22T19:47:22Z
dc.date.issued2022
dc.departmentBelirleneceken_US
dc.description.abstractLncRNAs are associated with malignancies with their tumor suppressor/oncogenic properties. Although many studies are conducted related to the mechanism of action for dasatinib and ponatinib in chronic myeloid leukemia (CML), their comparative effects on lncRNA expressions are largely unknown. Hence, we aimed to define the lncRNAs involved in the treatment of CML with dasatinib and ponatinib. We measured the cytotoxicities of dasatinib/ponatinib with CCK-8 assay and identified differentially expressed lncRNAs (DEL) by qRT-PCR. We determined the principal functions of DELs by Ingenuity Pathway Analysis (IPA) and performed gene ontology (GO) analysis for apoptosis and anti-proliferation-related lncRNAs. Apoptotic and anti-proliferative activities of dasatinib/ponatinib were confirmed by flow-cytometry. In K562 cells, dasatinib/ponatinib re-regulated lncRNAs which were dysregulated in leukemia. DELs after treatment (forty with dasatinib, thirty-seven with ponatinib) were related to increased cell death; decreased cell viability, proliferation, tumor growth, invasion, migration. Dasatinib-mediated network was related to cancer, hematological disease while ponatinib-mediated network was associated with cancer, cell death/survival, cell-to-cell signaling/interaction. Both treatments predicted activation of IFN gamma, IL1 beta, TNF as upstream regulators, specially this effect was higher in dasatinib. Comparison analysis showed that ponatinib was predicted more effective in cell death of tumor cell line than dasatinib. We confirmed that ponatinib was more potent than dasatinib to induce apoptosis and inhibit proliferation of CML cells, in consensus with IPA and GO analysis results. LncRNAs are specifically involved in anti-leukemic activities of dasatinib and ponatinib. Our findings will contribute to understanding signalization occurring in CML cells after standard treatments.en_US
dc.identifier.doi10.1007/s12032-021-01629-0
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue3en_US
dc.identifier.pmid35059859en_US
dc.identifier.scopus2-s2.0-85123282785en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s12032-021-01629-0
dc.identifier.urihttps://hdl.handle.net/20.500.14034/663
dc.identifier.volume39en_US
dc.identifier.wosWOS:000745033700003en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherHumana Press Incen_US
dc.relation.journalMedical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectChronic myeloid leukemiaen_US
dc.subjectLong non-coding RNAen_US
dc.subjectTyrosine kinase inhibitorsen_US
dc.subjectIngenuity pathway analysisen_US
dc.subjectCell deathen_US
dc.subjectCell proliferationen_US
dc.subjectLong Noncoding Rnasen_US
dc.subjectBcr-Abl Inhibitoren_US
dc.subjectTyrosine Kinaseen_US
dc.subjectStem-Cellsen_US
dc.subjectCml Stemen_US
dc.subjectResistanceen_US
dc.subjectApoptosisen_US
dc.subjectSurvivalen_US
dc.subjectImatiniben_US
dc.subjectCanceren_US
dc.titleComparative expression analysis of dasatinib and ponatinib-regulated lncRNAs in chronic myeloid leukemia and their network analysisen_US
dc.typeArticleen_US

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