Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275502 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1804980.fastq.gz | Fastqsanger.gz | |||
| SRR1804981.fastq.gz | Fastqsanger.gz | |||
| SRR1804982.fastq.gz | Fastqsanger.gz | |||
| SRR1804979.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress, limiting neurodegeneration and maintaining normal lifespan in eukaryotes. However, the molecular function of OXR1 is still unknown. Previously we showed that human OXR1 regulates expression of antioxidant genes GPX2 and HO-1 via the p21 signaling pathway. To examine the role of hOXR1 in global transcription regulation during cellular stress, we employed RNA sequencing to investigate the transcription profile in hOXR1 depleted HeLa cells. Methods: Control siRNA (siCon) and human OXR1 siRNA (siOXR1) transfected HeLa cells were either harvested directly (siCon_NT, siOXR1_NT) or exposed to 0.5 mM H2O2 for 1 h and then harvested immediately without recovery (siCon_R0h, siOXR1_R0h). Total RNA pooled from duplicate samples was used for RNA sequencing on an Illumina HiSeq2000 platform. The sequence reads that passed quality filters were analyzed at gene level. The Blast2GO program was used to generate gene ontology (GO) annotation of differentially expressed genes (DEGs).The WEGO software was used to further perform GO functional classification and to predict pathways affected. qRTM-bM-^@M-^SPCR validation was performed using SYBR Green assays. Results: In total, in non-treated and hydrogen peroxide exposed cells, hOXR1 depletion results in the down-regulation of 554 genes and the up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and p21) and apoptosis (i.e. CytC and CASP9). Western blot analysis reveals that hOXR1 suppresses CASP9 protein expression and reduces post-translational cleavage into its active form. After exposure to hydrogen peroxide (1 h), 56 early response genes were up-regulated in hOXR1 depleted cells, in which 38 of these genes were not induced in control cells. In addition, a subset of the commonly up-regulated early response genes showed a stronger induction in hOXR1 depleted cells (i.e. FOS, JUN and DUSP1). Out of a total of 52 differentially expressed transcription factors in hOXR1 depleted cells under normal physiology and oxidative stress condition, 14 genes (including HIF1A, STAT5A, E2F8 and TCF3) are differentially regulated under H2O2 treatment in hOXR1 silenced cells as compared to control cells. Finally, we demonstrate that hOXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress. Conclusions: Human OXR1 is important for regulation of the early stress response to oxidative stress in HeLa cells. HOXR1 modulates the p53 signaling pathway via regulation of genes involved in cell cycle arrest, apoptosis and anti-oxidation. Further, hOXR1 regulates numerous transcription factors of importance for cellular stress responses. In summary, hOXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species (ROS) and modulate cell cycle arrest and cell death (apoptosis). The mRNA profiles of hOXR1 depleted and control Hela cells with or without H2O2 treatment 1 h were generated by RNA sequencing using Illumina Hiseq 2000.
2015-02-16 | E-GEOD-65949 | biostudies-arrayexpress
Project description:Purpose: The oxidation resistance gene 1 (OXR1) is crucial for protecting against oxidative stress, limiting neurodegeneration and maintaining normal lifespan in eukaryotes. However, the molecular function of OXR1 is still unknown. Previously we showed that human OXR1 regulates expression of antioxidant genes GPX2 and HO-1 via the p21 signaling pathway. To examine the role of hOXR1 in global transcription regulation during cellular stress, we employed RNA sequencing to investigate the transcription profile in hOXR1 depleted HeLa cells. Methods: Control siRNA (siCon) and human OXR1 siRNA (siOXR1) transfected HeLa cells were either harvested directly (siCon_NT, siOXR1_NT) or exposed to 0.5 mM H2O2 for 1 h and then harvested immediately without recovery (siCon_R0h, siOXR1_R0h). Total RNA pooled from duplicate samples was used for RNA sequencing on an Illumina HiSeq2000 platform. The sequence reads that passed quality filters were analyzed at gene level. The Blast2GO program was used to generate gene ontology (GO) annotation of differentially expressed genes (DEGs).The WEGO software was used to further perform GO functional classification and to predict pathways affected. qRT–PCR validation was performed using SYBR Green assays. Results: In total, in non-treated and hydrogen peroxide exposed cells, hOXR1 depletion results in the down-regulation of 554 genes and the up-regulation of 253 genes. These differentially expressed genes include transcription factors (i.e. HIF1A, SP6, E2F8 and TCF3) and numerous genes of the p53 signaling pathway involved in cell-cycle arrest (i.e. cyclin D, CDK6 and p21) and apoptosis (i.e. CytC and CASP9). Western blot analysis reveals that hOXR1 suppresses CASP9 protein expression and reduces post-translational cleavage into its active form. After exposure to hydrogen peroxide (1 h), 56 early response genes were up-regulated in hOXR1 depleted cells, in which 38 of these genes were not induced in control cells. In addition, a subset of the commonly up-regulated early response genes showed a stronger induction in hOXR1 depleted cells (i.e. FOS, JUN and DUSP1). Out of a total of 52 differentially expressed transcription factors in hOXR1 depleted cells under normal physiology and oxidative stress condition, 14 genes (including HIF1A, STAT5A, E2F8 and TCF3) are differentially regulated under H2O2 treatment in hOXR1 silenced cells as compared to control cells. Finally, we demonstrate that hOXR1 depleted cells undergo cell cycle arrest in G2/M phase during oxidative stress. Conclusions: Human OXR1 is important for regulation of the early stress response to oxidative stress in HeLa cells. HOXR1 modulates the p53 signaling pathway via regulation of genes involved in cell cycle arrest, apoptosis and anti-oxidation. Further, hOXR1 regulates numerous transcription factors of importance for cellular stress responses. In summary, hOXR1 may act as a sensor of cellular oxidative stress to regulate the transcriptional networks required to detoxify reactive oxygen species (ROS) and modulate cell cycle arrest and cell death (apoptosis).
2015-02-16 | GSE65949 | GEO
Project description:Apoptosis of vascular smooth muscle cells (VSMCs) is closely related to the pathogenesis of cardiovascular disease, and oxidative stress is an important cause for VSMCs death. Inhibiting VSMCs apoptosis is an effective preventive strategy in slowing down the development of cardiovascular disease, especially for atherosclerosis. In this study, we found OXR1 (oxidation resistance protein 1), a crucial participator for responding for oxidative stress, could modulate the expression of p53, a key regulator of apoptosis. Our results revealed that oxidative stress promoted VSMCs apoptosis by overexpression of OXR1-p53 axis, and 6-shogaol (6S), a major biologically active compound present in ginger, could effectively attenuate cell death by preventing the up-regulated expression of OXR1-p53 axis. Quantitative proteomics analysis revealed that the degradation of p53 mediated by OXR1 might related with the enhanced assembly of SCF ubiquitin ligase complexes, which is reported to closely relate with the modification of ubiquitination or neddylation, and subsequent degradation of p53.
2022-02-22 | PXD015127 | Pride
Project description:To elucidate the regulatory mechanisms of AIMP3 for the pluripotency and differentiation in mESCs, we performed a microarray analysis in control and AIMP3-depleted mESCs. Compared to control, 1,279 genes were significantly up or down-regulated (1.5 fold, p<0.05) in AIMP3-depleted cells. Through analysis with DAVID bioinformatics online tolls, the p53 signaling pathway was found to be activated in AIMP3-depleted cells. Alterations of p53 signaling pathway-related genes were confirmed by real-time PCR.
2017-09-27 | GSE104241 | GEO
Project description:Purpose: The Oxidation Resistance 1 gene (OXR1) confers neuroprotection against oxidative stress. Oxr1 deficiency in mice resulted in cerebellar neurodegeneration. Genetic causes account for the most proportion of neurodegenerative disorders (early) onset in children. However, the pathological consequence of Oxr1 deficiency in human remains unclear. To assess the effect of OXR1 on the whole transcriptome during neuronal differentiation, we conducted RNA-sequencing of iPS cells, neural aggregates and neurons derivated from OXR1 deficient patient fibroblast and compared with healthy control. Methods: The iPS cells (iPSC) were generated from fibroblast cells of health control (WT) and OXR1 deficient patient (OX), and induced 2 days to form neural aggregate (NA) following to be differentiated into neuron cells in day 20. Total RNA was pooled from triplicate samples in each group and performed RNA sequencing on an Illumina HiSeq2500 platform. The sequence reads that passed quality filters were analyzed at gene level. The GOseq program was used to generate gene ontology (GO) annotation of differentially expressed genes (DEGs). The pathway enrichments were identified by KEGG Pathway Enrichment Analysis. qRT–PCR validation was performed using SYBR Green assays. Results:Totally 1595 DEGs were identified at neuron stage due to Oxr1 disruption, 874 DEGs at iPSC stage and 388 DEGs at NA stage. Among them, there are 61 DEGs commonly regulated by Oxr1 throughout all of the three stages . Further gene oncology (GO) analysis of biological process showed there was a significant enrichment for DEGs related to cell adhesion and extracellular matrix organization (ECM), cell development, cell differentiation, organ development caused by Oxr1 deficiency throughout all developmental stages. Especially neurogenesis and differentiation, axonogensis and guidance, brain and nerves system development were among the top of 50 items when entering neuron stage. In addition, a set of DEGs was significantly enriched in positive regulation of intrinsic apoptotic signaling pathway and regulation of cellular response to stress. Conclusions: Oxr1 regulates transcriptional networks required for modulating oxidative stress, apoptosis and neurogenesis during neuronal differentiation of iPS cells.
2025-02-18 | GSE86426 | GEO
Project description:We report a loss-of-function mutation in the TLDc domain of human Oxidation Resistance 1 (OXR1) gene, resulting in early-onset epilepsy, developmental delay, cognitive disabilities, and cerebellar atrophy. Patient lymphoblasts show impaired cell survival, proliferation, and hypersensitivity to oxidative stress. These phenotypes are rescued by TLDc domain replacement. We generated patient derived induced pluripotent stem cells (iPSCs) revealing impaired neural differentiation along with dysregulation of genes essential for neurodevelopment. We identified that OXR1 influences histone arginine methylation by activating protein arginine methyltransferases (PRMTs), suggesting OXR1 dependent mechanisms regulating gene expression during neurodevelopment. We modeled the function of OXR1 in early human brain development using patient derived brain organoids revealing that OXR1 contributes to the spatial-temporal regulation of histone arginine methylation in specific brain regions. Our work provides new insights into pathological features and molecular underpinnings associated with OXR1 deficiency, highlighting the therapeutic potential of OXR1 in numerous neurodegenerative and neurodevelopmental disorders.
2023-04-06 | GSE206614 | GEO
Project description:Transcriptome analysis of control and MALAT1 lncRNA-depleted RNA samples from human diploid lung fibroblasts [WI38] The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or pre-mRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation. We analyzed RNA from control and MALAT1 depleted WI38 cells using the Affymetrix Human Exon 1.0 ST platform. Array data was analyzed by Partek Genomic Suite software.
2013-01-29 | E-GEOD-43830 | biostudies-arrayexpress
Project description:The goal of this experiment was to determine the role of the lncRNA DINO in the DNA damage response in regulating transcription factor occupancy of human fibroblasts. DINO, an inducible long noncoding in respose to DNA damage, is required for cell cycle arrest and induction of several p53 regulated genes. We hypothesized that ATACseq in DINO-depleted cells may uncover a role for DINO in transcription factor recruitment to p53 responsive genes following DNA damage.
2016-09-26 | GSE76417 | GEO
Project description:Transcriptome analysis of control and MALAT1 lncRNA-depleted RNA samples from human diploid lung fibroblasts [WI38] The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or pre-mRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation.
2013-01-29 | GSE43830 | GEO
Project description:To test the hypothesis that circRNAs might encode functional peptides in mammalian cells, we studied the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT), which was previously reported as a tumor suppressor and connected p53 activation with polycomb repressive complex 2 (PRC2). We selected this long noncoding RNA (lncRNA) for further analysis because LINC-PINT has a long exon 2 which in accordance with the bioinformatical analyzed circular RNA standard.The following immunoblotting showed 87aa peptide level also decreased, indicating that this peptide is encoded by circPINTexon2. We name this circRNA encoded peptide PINT87aa. To investigate the possible regulatory role of PINT87aa, we did the expression micro array in PINT87aa stably transfect U251 or U87 glioblastoma cells and their control cells. The array analysis reveals that PINT87aa may involve in the cell cycle regulation, anti-apoptosis effects and multiple oncogenic signaling pathway activation.
2015-11-04 | E-GEOD-74610 | biostudies-arrayexpress