RNA sequencing analysis in ESCC cells with Drp1 overexpression or TFAM deficiency
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ABSTRACT:
PROVIDER: PRJNA757454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15600838_1.fastq.gz | Fastqsanger.gz | |||
| SRR15600838_2.fastq.gz | Fastqsanger.gz | |||
| SRR15600840_1.fastq.gz | Fastqsanger.gz | |||
| SRR15600840_2.fastq.gz | Fastqsanger.gz | |||
| SRR15600841_1.fastq.gz | Fastqsanger.gz |
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Project description:Mitochondrial homeostasis is important for cell metabolism, growth, proliferation, and immune responses. The critical regulator for mitochondrial homeostasis, Drp1 and TFAM are frequently abnormal expression in many cancers and is closely implicated in tumorigenesis. Here, we found that Drp1 high expression or TFAM low expression is correlated with poor overall survival of ESCC patients. However, the underling mechanism by Drp1 or TFAM influence tumor progression is largely unknown, especially in esophageal squamous cell carcinoma (ESCC). To investigate the underling mechanisms of Drp1 overexpression or TFAM deficiency-mediated ESCC progression, transcriptome profiling was performed by RNA sequencing analysis in ESCC cells with Drp1 overexpression or TFAM knockdown.
2022-03-02 | GSE182710 | GEO
Project description:Purpose:to verify Drp1-mediated biological pathways under physiological and ischemia conditions.Methods:C57BL/6 mice and Drp1 knockdown mice were used for ischemia treatment. Right femoral arteries were catheterized with polyethylene catheters for bleeding 50% of total blood volume (≈7% of weight). The ischemia time started to calculate after the model was established. A laparotomy was then carried out to obtain superior mesenteric artery tissues (SMAs) for transcriptome analysis. Series-Cluster analysis was performed to identify the global trends of mitochondrial DEGs after Drp1 knockdown. Gene ontology (GO) analysis was performed to facilitate elucidating the biological process (BP), molecular function (MF) and cellular component (CC) of unique genes in the significant or representative profiles. Results:In addition to its traditional roles in GTPase regulation and mitochondrial fission, Drp1 may also regulate actin cytoskeleton and the movement of microtubules. Besides, Drp1 may participate in the regulation of morphology and functions of other organelles, including endoplasmic reticulum, peroxisome, phagolysosome, etc. As for general organ functions, Drp1 may regulate vascular constriction and dilation. These consequences indicated the important role of Drp1 in ischemia-induced cellular regulation. Conclusions: Drp1 deficiency proves the important role of Drp1 in ischemia-induced biomedical processes through multiple potential fission-independent manners. Methods:C57BL/6 mice and Drp1 knockdown mice were used for ischemia treatment. Right femoral arteries were catheterized with polyethylene catheters for bleeding 50% of total blood volume (≈7% of weight). The ischemia time started to calculate after the model was established. A laparotomy was then carried out to obtain superior mesenteric artery tissues (SMAs) for transcriptome analysis. Series-Cluster analysis was performed to identify the global trends of mitochondrial DEGs after Drp1 knockdown. Gene ontology (GO) analysis was performed to facilitate elucidating the biological process (BP), molecular function (MF) and cellular component (CC) of unique genes in the significant or representative profiles. Results:In addition to its traditional roles in GTPase regulation and mitochondrial fission, Drp1 may also regulate actin cytoskeleton and the movement of microtubules. Besides, Drp1 may participate in the regulation of morphology and functions of other organelles, including endoplasmic reticulum, peroxisome, phagolysosome, etc. As for general organ functions, Drp1 may regulate vascular constriction and dilation. These consequences indicated the important role of Drp1 in ischemia-induced cellular regulation. Conclusions: Drp1 deficiency proves the important role of Drp1 in ischemia-induced biomedical processes through multiple potential fission-independent manners.
2020-04-29 | GSE124096 | GEO
Project description:SIRT3 is a NAD+-dependent mitochondrial protein deacetylase participating in the regulation of central metabolism and mitochondrial proteostasis. SIRT3 is downregulated in clear cell renal cell carcinoma (ccRCC), a main type of renal cancers, but the function of SIRT3 in tumorigenesis and development of ccRCC remains unknown. In this study, we established a SIRT3 overexpressed cell line to explore the changes of proteomics and metabolomics regulated by SIRT3 expression. Both the results of quantitative proteomics, metabolomics and acetylome showed overexpression of SIRT3 increased mitochondrial biogenesis and reversed the mitochondrial dysfunctions in ccRCC. We found SIRT3 could increase the activity of TFAM through modulation of TFAM transcription, degradation and acetylation level. The acetylation of TFAM K154 decreased while TFAM protein expression increased after SIRT3 overexpression. Further study revealed that SIRT3 could bind with TFAM, and decrease the acetylation of TFAM, promoting TFAM activity in mitochondrial biogenesis. Overall, our results present a new mechanism of SIRT3 in regulating mitochondrial functions, and the downregulation of SIRT3 in ccRCC lowers the activity of TFAM, subsequently inhibits the transcription of mitochondrial genes and mitochondrial biogenesis.
2018-08-14 | PXD009110 | Pride
Project description:The goal of this analysis was to utilize microarray profiling to identify basal alterations in gene expression in response to TFAM depletion and mtDNA stress. Mitochondrial DNA (mtDNA) is normally present at thousands of copies per cell and is packaged into several hundred higher-order structures termed nucleoids. The abundant mtDNA-binding protein, TFAM (transcription factor A,mitochondrial), regulates nucleoid architecture, abundance and segregation. Complete mtDNA depletion profoundly impairs oxidative phosphorylation, triggering calcium-dependent stress signalling and adaptive metabolic responses. However, the cellular responses to mtDNA instability, a physiologically relevant stress observed in many human diseases and ageing, remain poorly defined. Here we show that moderate mtDNA stress elicited by TFAM deficiency engages cytosolic antiviral signalling to enhance the expression of a subset of interferon-stimulated genes. Mechanistically, we find that aberrant mtDNA packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor cGAS (also known as MB21D1) and promotes STING (also known as TMEM173)–IRF3-dependent signalling to elevate interferon-stimulated gene expression, potentiate type I interferon responses and confer broad viral resistance. Furthermore, we demonstrate that herpesviruses induce mtDNA stress, which enhances antiviral signalling and type I interferon responses during infection. Our results further demonstrate that mitochondria are central participants in innate immunity, identify mtDNA stress as a cell-intrinsic trigger of antiviral signaling and suggest that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully engage antiviral innate immunity. Murine embryonic fibroblasts were isolated from wild-type or Tfam+/- E13.5 littermate embryos. RNA from passage-matched wild-type and Tfam+/- MEF lines was extracted in duplicate and hybridized onto Affymetrix microarrays. Four arrays were performed in total with two technical replicates per genotype.
2015-01-26 | E-GEOD-63767 | biostudies-arrayexpress
Project description:In this report, we showed that TFAM deficiency caused impaired AM mitochondrial fitness, altered metabolism and defective lipid catabolic responses, leading to diminished AM quantity and altered AM phenotypes. We demonstrated that TFAM deficiency did not impair AM differentiation from their precursors, but caused reduced AM maintenance. RNA-seq experiment revealed that TFAM deficiency caused impaired AM self-renewal capability. We showed that TFAM deficiency in AMs caused impaired clearance of respiratory debris, surfactant and enhanced susceptibility to severe influenza virus infection. Finally, we found that influenza infection resulted in disruption of TFAM-mediated mitochondrial fitness and metabolism in AMs.
2021-11-07 | GSE188279 | GEO
Project description:Expression data from EI24 overexpression in ESCC cells
| PRJNA646230 | ENA
Project description:Mitochondrial transcription factor A (TFAM) is associated with a number of neurodegenerative diseases and also with asthma. TFAM deficiency-induced mitochondrial DNA stress primes the antiviral innate immune response in mouse embryonic fibroblasts. In this study, we overexpressed TFAM in human lung epithelial cells (A549), then obtained and analyzed the TFAM-regulated transcriptome by Illumina-sequencing technology. We found that TFAM overexpression down-regulated and up-regulated the expression 642 and 169 genes (DEGs), respectively. The TFAM-repressed genes were highly enriched in cytokine-mediated signaling pathway, type I interferon- and INFmediated signaling pathways, and viral response pathways. We also revealed that 2563 alternative splicing events in 1796 genes (ASG) were de-regulated upon TFAM overexpression. These TFAM-responding ASGs were strongly enriched in DNA repair, nerve growth factor receptor signaling pathway, and also transcription regulation. Further analysis revealed that the promoters of TFAM-repressed DEGs were enriched by DNA binding motifs of transcription factors whose alternative splicing regulated by TFAM. These findings suggested that TFAM regulates not only immune response gene expression in human lung epithelial cells, but also alternative splicing which may play a role in mediating transcriptional regulation. This TFAM-centered gene regulation network could be targeted in developing therapies against various diseases.
2021-12-15 | GSE162384 | GEO
Project description:ChIP-seq data characterizing the occupancy of TFAM over the mitochondrial and nuclear genomes in HeLa cells. Characterization of mitochondrial and nuclear genome-wide TFAM binding in HeLa cells
2013-09-21 | E-GEOD-48176 | biostudies-arrayexpress
Project description:Analysis of EC109 cells following overexpression of EI24 and control vector. Etoposide induced 2.4 kb transcript (EI24), also known as p53-induced gene 8 (PIG8), is located on human chromosome 11q23. Serving as a p53 responsive pro-apoptotic factor, EI24 plays a pivotal role in inhibiting cell growth and activating autophagy and is associated with drug resistance. Results provide insight into the role of EI24 in cell proliferation and drug resistance of ESCC cells.
2020-07-15 | GSE154422 | GEO
Project description:Background & Aims Mitochondrial dysfunction and mtDNA stress-mediated inflammasome activation play critical roles in the pathogenesis of dry eye disease (DED). Mitochondrial transcription factor A (TFAM) is essential for regulating mtDNA stability and mitochondrial homeostasis. However, the mechanism underling TFAM to infuence DED progression is largely unknown. As a cytosolic DNA sensor, absent in melanoma 2 (AIM2) may contribute to the development of DED. Therefore, we aimed to explore whether the role of TFAM is associated with AIM2 inflammasome activation in DED. Methods The changes in inflammation, mitochondrial function, mtDNA homeostasis and TFAM expression were analyzed in the corneas of DED mice in vivo and in HCECs under oxidative stress in vitro. The effects of TFAM knockout on mtDNA homeostasis, mitochondrial respiration and cytokine release were also investigated in HCECs. The mechanism was analyzed by RNA sequencing in the corneas of DED mice, which was further verified by the HCECs with TFAM depletion. Results We found that the corneas of DED mice and HCECs under oxidative stress exhibited inflammation, mitochondrial damage and mtDNA maintenance disruption , which were highly associated with significantly reduced TFAM protein levels. Furthermore, we demonstrated that silencing of TFAM in HCECs suppressed mitochondrial respiratory capacity, induced mtDNA released into the cytosol and triggered cytokine release. Mechanistically, cytosolic mtDNA accumulation caused by TFAM depletion activated the AIM2 inflammasome and facilitated inflammation, thereby driving DED progression. Conclusions Our findings elucidate that TFAM deficiency induces mitochondrial dysfunction and cytosolic mtDNA stress, which subsequently activates the AIM2 inflammasome, triggers inflammatory responses and promotes DED progression. TFAM pathway may provide a novel therapeutic strategy for DED.
2024-06-18 | GSE252984 | GEO