Transcriptome analysis of human OXR1 depleted cells reveals its role in regulating the p53 signaling pathway

Sci Rep. 2015 Nov 30;5:17409. doi: 10.1038/srep17409.

Abstract

The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown. We employed RNA sequencing to examine the role of human OXR1 for genome wide transcription regulation. In total, in non-treated and hydrogen peroxide exposed HeLa cells, OXR1 depletion resulted in down-regulation of 554 genes and up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3), antioxidant genes (PRDX4, PTGS1 and CYGB) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and RPRM) and apoptosis (i.e. CytC and CASP9). We demonstrated that OXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress and increase protein expression of the apoptosis initiator protease CASP9. In summary, OXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species and modulate cell cycle and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 9 / metabolism
  • Cell Cycle / genetics
  • Cell Cycle Checkpoints / genetics
  • Cluster Analysis
  • Computational Biology / methods
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Gene Ontology
  • HeLa Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mitochondrial Proteins
  • Oxidative Stress / genetics
  • Proteins / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Reproducibility of Results
  • Signal Transduction*
  • Stress, Physiological
  • Transcription Factors / metabolism
  • Transcriptome*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Mitochondrial Proteins
  • OXR1 protein, human
  • Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Caspase 9

Associated data

  • GEO/GSE65949