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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

The differential expression profile in hOXR1 depleted HeLa cells.The HeLa cells were transfected with control siRNA (siCon) or hOXR1 siRNA (siOXR1) and, split into six-well plate after one day. One day later cells were treated without (NT) or with 0.5 mM H2O2 for 1 h. Cells were harvested immediately without recovery (R0h). The total RNA was isolated and analyzed by RNA-seq. (a) Scattered plot of hOXR1-depleted cells show differentially expressed genes without (NT) or with peroxide treatment (+H2O2). (b) Venn diagram analysis of common/unique down- and up-regulated genes in hOXR1 depleted cells without (NT) or with peroxide treatment (+H2O2). (c) Heatmap showing the overview of total DEGs caused by hOXR1 depletion. Red: up regulation; green: down regulation; black: no change.
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f1: The differential expression profile in hOXR1 depleted HeLa cells.The HeLa cells were transfected with control siRNA (siCon) or hOXR1 siRNA (siOXR1) and, split into six-well plate after one day. One day later cells were treated without (NT) or with 0.5 mM H2O2 for 1 h. Cells were harvested immediately without recovery (R0h). The total RNA was isolated and analyzed by RNA-seq. (a) Scattered plot of hOXR1-depleted cells show differentially expressed genes without (NT) or with peroxide treatment (+H2O2). (b) Venn diagram analysis of common/unique down- and up-regulated genes in hOXR1 depleted cells without (NT) or with peroxide treatment (+H2O2). (c) Heatmap showing the overview of total DEGs caused by hOXR1 depletion. Red: up regulation; green: down regulation; black: no change.

Mentions: Differentially expressed genes in hOXR1 depleted cells. By comparing the RNA sequencing results from hOXR1 depleted cells and control cells we identified 807 differentially expressed genes (DEGs), in which 554 genes are down- regulated and 253 genes are up-regulated (Fig. 1). In non-treated hOXR1 depleted cells, we identified 485 down-regulated genes and 194 up-regulated genes as compared to the control cells (Fig. 1a) (Supplementary Table S2). After H2O2 treatment, we find 355 down-regulated genes and 193 up-regulated genes (Fig. 1a and Supplementary Table S3). Notably, comparing DEGs before and after treatment showed that 286 genes (51%) and 134 genes (53%) of the down- and up-regulated DEGs, respectively, were similarly regulated under both conditions (Fig. 1b,c). All together, these data suggest that hOXR1 has an important role in transcriptional regulation of numerous genes under normal physiology and during oxidative stress.


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)

The differential expression profile in hOXR1 depleted HeLa cells.The HeLa cells were transfected with control siRNA (siCon) or hOXR1 siRNA (siOXR1) and, split into six-well plate after one day. One day later cells were treated without (NT) or with 0.5 mM H2O2 for 1 h. Cells were harvested immediately without recovery (R0h). The total RNA was isolated and analyzed by RNA-seq. (a) Scattered plot of hOXR1-depleted cells show differentially expressed genes without (NT) or with peroxide treatment (+H2O2). (b) Venn diagram analysis of common/unique down- and up-regulated genes in hOXR1 depleted cells without (NT) or with peroxide treatment (+H2O2). (c) Heatmap showing the overview of total DEGs caused by hOXR1 depletion. Red: up regulation; green: down regulation; black: no change.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: The differential expression profile in hOXR1 depleted HeLa cells.The HeLa cells were transfected with control siRNA (siCon) or hOXR1 siRNA (siOXR1) and, split into six-well plate after one day. One day later cells were treated without (NT) or with 0.5 mM H2O2 for 1 h. Cells were harvested immediately without recovery (R0h). The total RNA was isolated and analyzed by RNA-seq. (a) Scattered plot of hOXR1-depleted cells show differentially expressed genes without (NT) or with peroxide treatment (+H2O2). (b) Venn diagram analysis of common/unique down- and up-regulated genes in hOXR1 depleted cells without (NT) or with peroxide treatment (+H2O2). (c) Heatmap showing the overview of total DEGs caused by hOXR1 depletion. Red: up regulation; green: down regulation; black: no change.
Mentions: Differentially expressed genes in hOXR1 depleted cells. By comparing the RNA sequencing results from hOXR1 depleted cells and control cells we identified 807 differentially expressed genes (DEGs), in which 554 genes are down- regulated and 253 genes are up-regulated (Fig. 1). In non-treated hOXR1 depleted cells, we identified 485 down-regulated genes and 194 up-regulated genes as compared to the control cells (Fig. 1a) (Supplementary Table S2). After H2O2 treatment, we find 355 down-regulated genes and 193 up-regulated genes (Fig. 1a and Supplementary Table S3). Notably, comparing DEGs before and after treatment showed that 286 genes (51%) and 134 genes (53%) of the down- and up-regulated DEGs, respectively, were similarly regulated under both conditions (Fig. 1b,c). All together, these data suggest that hOXR1 has an important role in transcriptional regulation of numerous genes under normal physiology and during oxidative stress.

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