Role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers
Peter Natesan Pushparaj1, Mahmood Rasool2, Muhammad Imran Naseer3
1Dr. Peter Natesan Pushparaj, PhD, Associate Professor, Center of Excellence in Genomic Medicine Research, Dept. of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
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 µM 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.
Insights
Next-generation knowledge discovery tools reveal bleomycin
Area of Science:
- Toxicogenomics
- Molecular Biology
- Pharmacology
Background:
- Understanding anticancer drug mechanisms is vital for assessing genotoxicity and side effects.
- Bleomycin's cellular, biomolecular, and toxicological functions require detailed examination.
Purpose of the Study:
- To investigate the cellular, molecular, and toxicological mechanisms of bleomycin using next-generation knowledge discovery (NGKD) tools.
- To identify key pathways and biological processes affected by bleomycin treatment.
Main Methods:
- Analysis of Toxicogenomic and DNA damage-inducing (TGx-DDI) gene expression data (GSE196373) from Gene Expression Omnibus (GEO).
- Utilized GEO2R and Linear Models for Microarray Analysis (limma) R packages to identify differentially expressed genes (DEGs).
- Employed iPathwayGuide to determine regulated signaling pathways, biological processes, molecular functions, and upstream regulators (genes and miRNAs).
Main Results:
- Bleomycin differentially regulates the p53 pathway, transcriptional dysregulation in cancer, FOXO pathway, viral carcinogenesis, and cancer pathways.
- Key biological processes affected include p53 class mediator signaling, intrinsic apoptotic signaling, and DNA damage response.
- iPathwayGuide analysis identified p53 and its regulatory gene and microRNA networks induced by bleomycin.
Conclusions:
- NGKD tools provide valuable insights into bleomycin's toxicogenomic mechanisms.
- Integrating multi-omics approaches is essential for developing biomarkers to evaluate anticancer drug safety and efficacy.
