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https://hdl.handle.net/20.500.14365/5453
Title: | Identification of Potential Inhibitors for Drug Resistance in Acute Lymphoblastic Leukemia Through Differentially Expressed Gene Analysis and in Silico Screening | Authors: | Özay, Başak Tükel, Ezgi Yağmur Ayna Duran, Gizem Kiraz, Yağmur |
Keywords: | Acute lymphoblastic leukemia Chemoresistance Drug screening Docking Transcriptomics Molecular dynamics Molecular-Dynamics Cell-Survival Force-Field Discovery Web Reveals Quality Biology Model Tool |
Publisher: | Academic press inc elsevier science | Abstract: | Acute lymphoblastic leukemia (ALL) is a disease of lymphocyte origin predominantly diagnosed in children. While its 5-year survival rate is high, resistance to chemotherapy drugs is still an obstacle. Our aim is to determine differentially expressed genes (DEGs) related to Asparaginase, Daunorubicin, Prednisolone, and Vincristine resistance and identify potential inhibitors via docking. Three datasets were accessed from the Gene Expression Omnibus database; GSE635, GSE19143, and GSE22529. The microarray data waes analyzed using R4.2.0 and Bioconductor packages, and pathway and protein-protein interaction analysis were performed. We identified 1294 upregulated DEGs, with 12 genes consistently upregulated in all four resistant groups. KEGG analysis revealed an association with the PI3K-Akt pathway. Among DEGs, 33 hub genes including MDM2 and USP7 were pinpointed. Within common genes, CLDN9 and HS3ST3A1 were subjected to molecular docking against 3556 molecules. Following ADMET analysis, three drugs emerged as potential inhibitors: Flunarizine, Talniflumate, and Eltrombopag. Molecular dynamics analysis for HS3ST3A1 indicated all candidates had the potential to overcome drug resistance, Eltrombopag displaying particularly promising results. This study promotes a further understanding of drug resistance in ALL, introducing novel genes for consideration in diagnostic screening. It also presents potential inhibitor candidates to tackle drug resistance through repurposing. | URI: | https://doi.org/10.1016/j.ab.2024.115619 https://hdl.handle.net/20.500.14365/5453 |
ISSN: | 0003-2697 1096-0309 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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