Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Induction of fatty acid oxidation underlies DNA damage-induced cell death and ameliorates obesity-driven chemoresistance

ABSTRACT: Induction of fatty acid oxidation underlies DNA damage-induced cell death and ameliorates obesity-driven chemoresistance

PROVIDER: PRJNA860379 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Induction of fatty acid oxidation underlies DNA damage-induced cell death and ameliorates obesity-driven chemoresistance

Project description:The DNA damage response is essential for preserving genome integrity and eliminating damaged cells. Although cellular metabolism plays a central role in cell fate decision between proliferation, survival or death, the metabolic response to DNA damage remains largely obscure. Here, we show that DNA damage induces fatty acid oxidation (FAO), which is required for DNA damage-induced cell death. Mechanistically, FAO induction increases cellular acetyl-CoA levels and promotes N-alpha-acetylation of caspase-2, leading to cell death. Whereas chemotherapy increases FAO related genes through PPARα, accelerated hypoxia-inducible factor-1α stabilization by tumor cells in obese mice impedes the upregulation of FAO, which contributes to its chemoresistance. Finally, we find that improving FAO by PPARα activation ameliorates obesity-driven chemoresistance and enhances the outcomes of chemotherapy in obese mice. These findings reveal the shift toward FAO induction is an important metabolic response to DNA damage and may provide effective therapeutic strategies for cancer patients with obesity.

2024-03-20 | GSE208632 | GEO

SIRT3 SUMOylation confers AML chemoresistance via down-regulation of HES1 dependent fatty acid oxidation

Project description:SIRT3 SUMOylation confers AML chemoresistance via down-regulation of HES1 dependent fatty acid oxidation

| PRJNA744391 | ENA

Anaerobic sulfur oxidation underlies adaptation of a chemosynthetic symbiont to oxic-anoxic interfaces

Project description:Anaerobic sulfur oxidation underlies adaptation of a chemosynthetic symbiont to oxic-anoxic interfaces

| PRJNA609171 | ENA

Analysing the Mechanism of Mitochondrial Oxidation-induced Cell Death Using a Multifunctional Iridium(III) Photosensitiser

Project description:Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena has not been defined. Here, we developed a multifunctional iridium(III) photosensitiser, Ir-OA, capable of inducing substantial mitochondrial oxidative stress and monitoring the corresponding change in viscosity, polarity, and morphology. Photoactivation of Ir-OA triggers chemical modifications in mitochondrial protein-crosslinking and oxidation (i.e., Oxidative phosphorylation complexes and channel and translocase proteins), leading to microenvironment changes, such as increased microviscosity and depolarisation. These changes are strongly related to cell death by inducing mitochondrial swelling with excessive fission and fusion. We suggest a potential mechanism from mitochondrial oxidative stress to cell death based on proteomic analyses and phenomenological observations.

2021-03-23 | PXD022163 | Pride

WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer

Project description:WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer

| PRJNA699435 | ENA

SIRT3 SUMOylation confers AML chemoresistance via down-regulation of HES1 dependent fatty acid oxidation

Project description:SIRT3 deacetylase is a critical mitochondrial regulator for mitochondrial metabolism reprogramming and ROS production, and is involved in the regulation of chemoresistance in AML. SIRT3 is a SUMOylated protein, with de-SUMOylation by SENP1, resulted in enhancement of its deacetylase activity. However, the molecular mechanism of de-SUMOylation mediated SIRT3 activation, which may lead to reinforced AML chemoresistance, remains poorly understood. In the current study, we demonstrated that SIRT3 SUMOylation was attenuated by cytarabine, and de-SUMOylation prevented SIRT3 from proteasome degradation. SIRT3 de-SUMOylation was capable of reprogramming mitochondrial biogenesis, and subsequently inhibited mitochondrial ROS production. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation, among which the transcription factor HES1, a downstream substrates of Notch1 signaling pathway, was significantly downregulated by SIRT3K288R, the de-SUMOylated and constitutively active mutant of SIRT3. HES1-dependent FAO was inhibited by SIRT3 de-SUMOylation. Moreover, cytarabine synergized with the SENP1 inhibitor momodrin-Ic to eradicate AML blasts in vitro and in xenografts mice models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in regulating chemoresistance in AML via HES1-dependent FAO, which may provide a rationale for SIRT3 SUMOylation-targeted intervention to improve the chemotherapies in AML.

2022-08-17 | GSE179617 | GEO

Sedanolide ameliorates hydrogen peroxide-induced apoptotic cell death via activation of KEAP1-NRF2 pathway

Project description:Sedanolide ameliorates hydrogen peroxide-induced apoptotic cell death via activation of KEAP1-NRF2 pathway

| PRJNA1028497 | ENA

Acetate oxidation

Project description:Acetate oxidation

| PRJNA1033353 | ENA

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma [RNA-seq]

Project description:Despite the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved the patients' survival and became the standard of care for advanced nasopharyngeal carcinoma (NPC), some patients could not benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, we identified ATMIN as a chemoresistance gene in response to TPF therapy in NPC patients. We found that USP10 deubiquitinates and stabilizes ATMIN protein. Knockdown of ATMIN inhibits the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells in vitro and in vivo. Mechanistically, RNA-seq combined with ChIP-seq analysis suggests that ATMIN is associated with the cell death signaling. ATMIN transcriptionally activates LCK to facilitate cell proliferation and docetaxel-resistance. Our findings broaden the insight into the mechanism of chemoresistance in NPC and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

2024-02-14 | GSE236504 | GEO

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma [ChIP-seq]

2024-02-14 | GSE236503 | GEO