Characterization of H2O2-Induced Alterations in Global Transcription of mRNA and lncRNA.

Shihua Liu,Peng Huang,Ya Qiu,Rong Xiang

doi:10.3390/antiox11030495

Shihua Liu, Peng Huang + Show 2 more

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https://doi.org/10.3390/antiox11030495

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Abstract

Hydrogen peroxide (H2O2) is an important reactive oxygen species that plays a major role in redox signaling. Although H2O2 is known to regulate gene expression and affect multiple cellular processes, the characteristics and mechanisms of such transcriptional regulation remain to be defined. In this study, we utilized transcriptome sequencing to determine the global changes of mRNA and lncRNA transcripts induced by H2O2 in human pancreatic normal epithelial (HPNE) and pancreatic cancer (PANC-1) cells. Promoter analysis using PROMO and TRRUST revealed that mRNAs and lncRNAs largely shared the same sets of transcription factors in response to ROS stress. Interestingly, promoters of the upregulated genes were similar to those of the downregulated transcripts, suggesting that the H2O2-responding promoters are conserved but they alone do not determine the levels of transcriptional outputs. We also found that H2O2 induced significant changes in molecules involved in the pathways of RNA metabolism, processing, and transport. Detailed analyses further revealed a significant difference between pancreatic cancer and noncancer cells in their response to H2O2 stress, especially in the transcription of genes involved in cell-cycle regulation and DNA repair. Our study provides new insights into RNA transcriptional regulation upon ROS stress in cancer and normal cells.

Highlights

Reactive oxygen species (ROS) encompass a group of chemically reactive molecules derived from molecular oxygen via reduction–oxidation reactions or electronic excitation [1]
We utilized the immortalized human pancreatic normal epithelial cell line hTERTHPNE and pancreatic cancer cell line PANC-1 to investigate their transcriptional response to ROS stress induced by H2 O2 treatment
The results showed that the transcription factors Nrf2, HIF-1α, ATM, NF-κB, and p53 were predicted as promoters of the upregulated long noncoding RNA (lncRNA), consistent with previously known transcription factors upon ROS stress

Summary

Introduction

Reactive oxygen species (ROS) encompass a group of chemically reactive molecules derived from molecular oxygen via reduction–oxidation (redox) reactions or electronic excitation [1]. Due to the increased metabolic demand for continuous proliferation, cancer cells often generate more ROS compared with normal cells [2]. A moderately elevated level of ROS may promote tumor cell proliferation, while extremely high concentrations of ROS can cause oxidative damage to proteins and nucleic acids, leading to cell death [3]. Controlling the balance between ROS and antioxidants is essential for cellular homeostasis, and targeting ROS metabolism could be an effective strategy to inhibit cancer cell growth as a therapeutic approach [4]. The fact that the use of antioxidants for treatment of diseases with oxidative stress often leads to limited success or even disappointing results suggests that a better understanding of redox signaling and its biological impact is required to provide a mechanistic basis for developing more effective therapeutic strategies

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