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

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.

Droplet‐Based Glycan and RNA Sequencing for Profiling the Distinct Cellular Glyco‐States in Single Cells

“…We also investigated the expression of MGAT3 in bulk samples of hTERT‐HPNE using a publicly available bulk RNA‐seq database and found a very low expression at 0–0.1 TPM (transcript per million). [ 9 ] This suggests that the detection of the MGAT3 gene expression in hTERT‐HPNE at the single‐cell level might be quite challenging. These findings indicate that it is not always easy to predict the glycan products on cell surfaces based solely on the expression of glycosyltransferase genes and that it is important to directly detect the expression of cell surface glycans using glycan‐binding probes.…”

“…Although the expression of the glycosyltransferase genes was very low, it was detectable. The 𝛼1-2fucosyltransferase genes (FUT1/2), 𝛼2-6sialyltransferase genes (ST6GAL1 and ST6GALNAC1-4), and N-acetylgalactosaminyl transferase genes (GALNT3, 5,6,7,9) were expressed higher in Panc04.03 cells than hTERT-HPNE cells (Figure 2g; Figures S6 and S7, Supporting Information). Therefore, we conclude that 𝛼1-2Fuc, 𝛼2-6Sia, and Tn antigens are expressed higher in PDAC cells (Panc04.03) than in normal pancreatic duct cells (hTERT-HPNE).…”

The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?

“…Long non-coding RNAs (LncRNAs) represent a prominent focus in contemporary cancer research, as it has the potential to produce aberrant peptide products that could serve as tumor antigens [167]. Intriguingly, recent findings have highlighted differential LncRNAs transcription responses to H 2 O 2 between normal and cancer cells, potentially elucidating variations in sensitivity to ROS between these cell types [168]. A significant portion of the differentially expressed LncRNAs are of the extronic type, and prominent transcription factors such as NRF2, HIF-1α, ataxia telangiectasia mutated (ATM), NF-κB, and p53 have been predicted as regulators of the upregulated LncRNAs.…”

“…A significant portion of the differentially expressed LncRNAs are of the extronic type, and prominent transcription factors such as NRF2, HIF-1α, ataxia telangiectasia mutated (ATM), NF-κB, and p53 have been predicted as regulators of the upregulated LncRNAs. This implies that these transcription factors not only govern the expression of protein-coding mRNAs, but also exert control over LncRNAs expression [168].…”

Multi-MXene assisted large-scale manufacturing of electrochemical biosensors based on enzyme-nanoflower enhanced electrodes for the detection of H2O2 secreted from live cancer cells

“…9 ROS are considered as important intracellular signaling molecules that regulate DNA damage, cellular apoptosis, protein synthesis, and other life activities. 10,11 The accumulation of excess ROS in live cells will lead to the disruption of intracellular activity and the generation of endogenous oxidative stress, disrupting the balance of normal cells or tissues and causing a variety of diseases including cancer, Alzheimer's disease, etc. 12,13 Generally, cancer cells overproduce ROS to maintain an active state and autocrine proliferative signals.…”