Comparative expression analysis of dasatinib and ponatinib-regulated lncRNAs in chronic myeloid leukemia and their network analysis
| Autor: | Cagla Kayabasi, Ayse Caner, Sunde Yilmaz Susluer, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Aycan Asik, Zeynep Mutlu, Cansu Caliskan Kurt, Bakiye Goker Bagca, Cigir Biray Avci, Fahri Sahin, Guray Saydam, Cumhur Gunduz |
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| Rok vydání: | 2021 |
| Předmět: |
Cell death
Cancer Research Stem-Cells Survival Bcr-Abl Inhibitor Cell Survival Resistance Ingenuity pathway analysis Dasatinib Apoptosis Tyrosine Kinase Long Noncoding Rnas Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive Humans Protein Kinase Inhibitors Cancer Cell Proliferation Tyrosine kinase inhibitors Chronic myeloid leukemia Imidazoles Hematology General Medicine Cml Stem Pyridazines Oncology Long non-coding RNA Imatinib RNA Long Noncoding K562 Cells Signal Transduction |
| Zdroj: | Medical oncology (Northwood, London, England). 39(3) |
| ISSN: | 1559-131X |
| Popis: | LncRNAs 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. |
| Databáze: | OpenAIRE |
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