Comparison of Oxidative and Hypoxic Stress Responsive Genes from Meta-Analysis of Public Transcriptomes.

Takayuki Suzuki,Hidemasa Bono,Yoko Ono

doi:10.3390/biomedicines9121830

Abstract

Analysis of RNA-sequencing (RNA-seq) data is an effective means to analyze the gene expression levels under specific conditions and discover new biological knowledge. More than 74,000 experimental series with RNA-seq have been stored in public databases as of 20 October 2021. Since this huge amount of expression data accumulated from past studies is a promising source of new biological insights, we focused on a meta-analysis of 1783 runs of RNA-seq data under the conditions of two types of stressors: oxidative stress (OS) and hypoxia. The collected RNA-seq data of OS were organized as the OS dataset to retrieve and analyze differentially expressed genes (DEGs). The OS-induced DEGs were compared with the hypoxia-induced DEGs retrieved from a previous study. The results from the meta-analysis of OS transcriptomes revealed two genes, CRIP1 and CRIP3, which were particularly downregulated, suggesting a relationship between OS and zinc homeostasis. The comparison between meta-analysis of OS and hypoxia showed that several genes were differentially expressed under both stress conditions, and it was inferred that the downregulation of cell cycle-related genes is a mutual biological process in both OS and hypoxia.

Highlights

Oxidative stress (OS) is characterized by an imbalance between oxidants and antioxidants, caused by an increase in the levels of reactive oxygen species (ROS) in a biological system
We collected 839 sets of RNA-seq data and curated them as the OS dataset with 386 pairs of OS and normal state transcriptome data
As OS is caused by various factors, sources of OS in the OS dataset include hydrogen peroxide (H2 O2 ), Ultra-Violet rays (UV), rotenone, lipopolysaccharide, arsenite, radiation, NF-E2-related factor-2 (NRF2) knockdown/KO, BRD4 KO, deoxynivalenol, palmitate, cadmium, methylmercury, zinc dimethyldithiocarbamate, aging, paraquat, and others (Table 1)

Summary

Introduction

Oxidative stress (OS) is characterized by an imbalance between oxidants and antioxidants, caused by an increase in the levels of reactive oxygen species (ROS) in a biological system. Due to its strong relationship with human health, the mechanisms of OS have been extensively investigated to provide biological and medical knowledge These include the mechanism of DNA damage by the highly reactive hydroxyl radicals, the role of OS in the appearance of carcinogenesis and the increase in OS-inducible inflammatory cells by activation of specific transcription factors such as NF-E2-related factor-2 (NRF2) [6,7]. The present study focused on analyzing the common features among various sources of OS from the perspective of changes in gene expression. As for another underdeveloped area of OS studies, a clear line between other types of stresses and OS has not been defined. It is necessary to compare OS and other stresses such as hypoxia, which is an oxygen-related stress condition

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Conclusion