Activation of PPARa suppresses metastasis of hepatocellular carcinoma in a high-fat diet context by reducing neutrophil extracellular traps release
| Title | Activation of PPARa suppresses metastasis of hepatocellular carcinoma in a high-fat diet context by reducing neutrophil extracellular traps release |
|---|---|
| Description | In this study, the molecular mechanism of NETs release and the potential improvement of the HCC microenvironment by PPARα agonists were explored through the utilization of proteomics, metabolomics, tissue microarray, immunofluorescence, flow cytometry, western blotting, and dual-luciferase reporter gene assay. Our study demonstrated a notable inhibition of PPARα signaling in HCC. Furthermore, the disruption of PPARα-mediated lipid metabolism was responsible for the release of NETs. The presence of HFD was observed to induce mitochondrial impairment in neutrophils, leading to the activation of cGAS-STING by oxidized mitochondrial DNA (Ox-mtDNA). Consequently, this activation triggered the release of NETs containing Ox-mtDNA through the enhancement of NLRP3-GSDMD-N in a NF-κB-dependent manner. Moreover, the release of NETs within HCC tissues effectively isolated cytotoxic leukocytes in the outer regions of HCC cells. |
| Organism | Homo sapiens |
| Data Type | Metabolome Data by Mass Spectrometry (MS) |
| Data Accessibility | Open-access |
| BioProject | PRJCA027835 |
| Release Date | 2024-10-29 |
| Submitter | Banglun Pan (1335563838@qq.com) |
| Organization | Fujian Medical University Union Hospital |
| Submission Date | 2024-07-08 |
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| File ID | File Title | Number/Samples | File Type | File Size | File Suffix | Download Times | Download |
|---|---|---|---|---|---|---|---|
| OMIX006828-01 | Metabolomics of hepatocellular carcinoma and paired tissue | 96 | Metabolome Data by Mass Spectrometry (MS) | 11.09 GB | zip | 0 |