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Defining the role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis using next-generation knowledge discovery method
被引：1
|作者：
Pushparaj, Peter Natesan
[1
]
Rasool, Mahmood
[1
]
Naseer, Muhammad Imran
[1
]
Gauthaman, Kalamegam
[1
,2
]
机构：
[1] King Abdulaziz Univ, Fac Appl Med Sci, Ctr Excellence Genom Med Res, Dept Med Lab Technol, Jeddah, Saudi Arabia
[2] Saveetha Inst Med & Tech Sci, Saveetha Dent Coll & Hosp, Ctr Transdisciplinary Res, Dept Pharmacol, Chennai, India
关键词：
Toxicogenomics;
Anticancer drugs;
TK6;
cells;
DNA damage;
Bleomycin;
iPathwayGuide;
Gene ontology;
Cell death;
Apoptosis;
Next generation knowledge discovery methods;
PATHWAY;
D O I：
10.12669/pjms.39.2.7321
中图分类号：
R5 [内科学];
学科分类号：
1002 ;
100201 ;
摘要：
Objectives: Accurately identifying the cellular, biomolecular, and toxicological functions of anticancer drugs help to decipher the potential risk of genotoxicity and other side effects. Here, we examined bleomycin for cellular, molecular and toxicological mechanisms using next-generation knowledge discovery (NGKD) tools.Methods: This study was conducted at the Faculty of Applied Medical Sciences, King Abdulaziz University (KAU), Jeddah, Saudi Arabia in October 2022. We first analyzed the raw Toxicogenomic and DNA damage-inducing (TGx-DDI) gene expression data from Gene Expression Omnibus (GEO) (GSE196373) of TK6 cells treated with 10 mu M bleomycin and TK6 cells treated with DMSO for four hours using the GEO2R tool based on the Linear Models for Microarray Analysis (limma) R packages to derive the differentially expressed genes (DEGs). Then, iPathwayGuide was used to determine differentially regulated signaling pathways, biological processes, cellular, molecular functions and upstream regulators (genes and miRNAs).Results: Bleomycin differently regulates the p53 pathway, transcriptional dysregulation in cancer, FOXO pathway, viral carcinogenesis, and cancer pathways. The biological processes such as p53 class mediator signaling, intrinsic apoptotic signaling, DNA damage response, and DNA damage-induced intrinsic apoptotic signaling and molecular functions like ubiquitin protein transferase and p53 binding were differentially regulated by bleomycin. iPathwayGuide analysis showed that the p53 and its regulatory gene and microRNA networks induced by bleomycin.Conclusion: Analysis of TGx-DDI data of bleomycin using NGKD tools provided information about toxicogenomics and other mechanisms. Integration of all "omics" based approaches is crucial for the development of translatable biomarkers for evaluating anticancer drugs for safety and efficacy.
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页码：423 / 429
页数：7
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