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

Yang M, Lin X, Rowe A, Rognes T, Eide L, Bjørås M - Sci Rep (2015)

Bottom Line: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, Norway.

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.

No MeSH data available.


Related in: MedlinePlus

Gene expression for a subset of genes in the p53 signaling pathway was impaired by hOXR1 depletion under physical conditions.The p53 pathway is adapted from KEGG database. The up-regulated genes are labeled in red, while the down-regulated genes are labeled in green.
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f3: Gene expression for a subset of genes in the p53 signaling pathway was impaired by hOXR1 depletion under physical conditions.The p53 pathway is adapted from KEGG database. The up-regulated genes are labeled in red, while the down-regulated genes are labeled in green.

Mentions: The Kyoto Encyclopedia of genes and Genomes (KEGG)13 pathway enrichment analysis showed that various pathways were affected by hOXR1 depletion in HeLa cells. In non-treated cells, the top 10 pathways include p53 signaling (Fig. 3), arachidonic acid metabolism and ECM (the extracellular matrix)-receptor interaction; while under oxidative stress, the top 10 pathways also contain p53 signaling pathway and arachidonic acid metabolism, but not ECM-receptor interaction (Supplementary Table S6). In addition, several other signaling pathways are also differentially regulated after hOXR1 depletion, such as the Hedgehog signaling, Nod (nucleotide-binding oligomerization domain containing) -like receptor signaling pathway (Supplementary Fig. S1), MAPK (mitogen-activated protein kinase) signaling, Notch signaling pathway, PPAR (peroxisome proliferator-activated receptor) signaling pathway and ErbB (epidermal growth factor receptor) signaling.


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

Yang M, Lin X, Rowe A, Rognes T, Eide L, Bjørås M - Sci Rep (2015)

Gene expression for a subset of genes in the p53 signaling pathway was impaired by hOXR1 depletion under physical conditions.The p53 pathway is adapted from KEGG database. The up-regulated genes are labeled in red, while the down-regulated genes are labeled in green.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663793&req=5

f3: Gene expression for a subset of genes in the p53 signaling pathway was impaired by hOXR1 depletion under physical conditions.The p53 pathway is adapted from KEGG database. The up-regulated genes are labeled in red, while the down-regulated genes are labeled in green.
Mentions: The Kyoto Encyclopedia of genes and Genomes (KEGG)13 pathway enrichment analysis showed that various pathways were affected by hOXR1 depletion in HeLa cells. In non-treated cells, the top 10 pathways include p53 signaling (Fig. 3), arachidonic acid metabolism and ECM (the extracellular matrix)-receptor interaction; while under oxidative stress, the top 10 pathways also contain p53 signaling pathway and arachidonic acid metabolism, but not ECM-receptor interaction (Supplementary Table S6). In addition, several other signaling pathways are also differentially regulated after hOXR1 depletion, such as the Hedgehog signaling, Nod (nucleotide-binding oligomerization domain containing) -like receptor signaling pathway (Supplementary Fig. S1), MAPK (mitogen-activated protein kinase) signaling, Notch signaling pathway, PPAR (peroxisome proliferator-activated receptor) signaling pathway and ErbB (epidermal growth factor receptor) signaling.

Bottom Line: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress; however, its molecular function is unknown.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Oslo University Hospital and University of Oslo, Norway.

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.

No MeSH data available.


Related in: MedlinePlus