Yazar "Eraslan, Serpil" seçeneğine göre listele

Listeleniyor 1 - 2 / 2
  • Küçük Resim Yok
    Öğe
    Insights Into the Mechanism of Anticancer Drug Imatinib Revealed Through Multi-Omic Analyses in Yeast
    (Mary Ann Liebert, Inc, 2020) Taymaz-Nikerel, Hilal; Eraslan, Serpil; Kirdar, Betul
    Imatinib mesylate is a receptor tyrosine kinase inhibitor drug with broad applications in cancer therapeutics, for example, in chronic myeloid leukemia and gastrointestinal stromal tumors. In this study, new multi-omics findings in yeast on the mechanism of imatinib are reported, using the model organismSaccharomyces cerevisiae. Whole-genome analysis of the transcriptional response of yeast cells following long-term exposure to imatinib, flux-balance analysis (FBA), and modular analysis of protein/protein interaction network consisting of proteins encoded by differentially expressed genes (DEGs) were performed. DEGs indicated that carbon, nitrogen, starch, sucrose, glyoxylate/dicarboxylate metabolism, valine and leucine degradation, and tricarboxylic acid cycle (TCA) were significantly upregulated. By contrast, ribosome biogenesis, pentose/glucuronate interconversion, tryptophan/pyruvate metabolic pathways, and meiosis were significantly downregulated. FBA revealed that a large set of metabolic pathways was altered by imatinib to compensate cancer-associated metabolic changes. Integration of transcriptome and interactome (protein/protein interactions) data helped to identify the core regulatory genes and pathways through elucidation of the active subnetworks. It appears that imatinib may also contribute to antitumoral immune response in the tumor microenvironment and most of the metabolic rearrangements are at posttranscriptional level. Furthermore, additional support for possible contribution of thiamine/pyridoxal phosphate biosynthesis and mitogen-activated protein kinase pathway to drug resistance is noted. This report advances multi-omics understanding of the mechanism of imatinib, and by extension, offers new molecular avenues toward precision medicine and discovery of novel drug targets in cancer therapeutics.
  • Küçük Resim Yok
    Öğe
    Time-dependent re-organization of biological processes by the analysis of the dynamic transcriptional response of yeast cells to doxorubicin
    (Royal Soc Chemistry, 2021) Karabekmez, Muhammed Erkan; Taymaz-Nikerel, Hilal; Eraslan, Serpil; Kirdar, Betul
    Doxorubicin is an efficient chemotherapeutic reagent in the treatment of a variety of cancers. However, its underlying molecular mechanism is not fully understood and several severe side effects limit its application. In this study, the dynamic transcriptomic response of Saccharomyces cerevisiae cells to a doxorubicin pulse in a chemostat system was investigated to reveal the underlying molecular mechanism of this drug. The clustering of differentially and significantly expressed genes (DEGs) indicated that the response of yeast cells to doxorubicin is time dependent and may be classified as short-term, mid-term and long-term responses. The cells have started to reorganize their response after the first minute following the injection of the pulse. A modified version of Weighted Gene Co-expression Network Analysis (WGCNA) was used to cluster the positively correlated co-expression profiles, and functional enrichment analysis of these clusters was carried out. DNA replication and DNA repair processes were significantly affected and induced 60 minutes after exposure to doxorubicin. The response to oxidative stress was not identified as a significant term. A transcriptional re-organization of the metabolic pathways seems to be an early event and persists afterwards. The present study reveals for the first time that the RNA surveillance pathway, which is a post-transcriptional regulatory pathway, may be implicated in the short-term reaction of yeast cells to doxorubicin. Integration with regulome revealed the dynamic re-organization of the transcriptomic landscape. Fhl1p, Mbp1p, and Mcm1p were identified as primary regulatory factors responsible for tuning the differentially expressed genes.