PLIN1 suppresses glioma progression through regulating lipid metabolism
Glioma is a common and destructive brain tumor, which is highly heterogeneous with poor prognosis. Developing diagnostic and prognostic markers to identify and treat glioma early would significantly improve the therapeutic outcomes. Here, we conducted RNA next-generation sequencing with 33 glioma samples and 15 normal brain samples. We found Perilipin 1 (PLIN1) downregulated in glioma and correlated with poorer outcome. Subsequent experiments revealed that up regulation of PLIN1 led to repressed cell growth and invasion in glioma. Moreover, overexpression of PLIN1 increased lipid accumulation in glioma cells, with increasing expression of lipid biosynthesis related genes and decreasing expression of lipolysis related genes. Mechanically, we revealed that the PI3K/AKT axis could regulate PLIN1 levels in glioma, that inhibition of the activity of PI3K/AKT axis could increase PLIN1 levels in glioma. In conclusion, the dysregulation PI3K/AKT axis led to PLIN1 downregulation and the following tumor proliferation, invasion and lipid metabolism reprogramming in glioma.
Authors
- Kai Zhuang (ORCID: https://orcid.org/0000-0003-1724-6210)
- Yuanbing Chen
- Fan Yang (ORCID: https://orcid.org/0000-0003-3160-8652)
- Kui Luo
- Yi Liu (ORCID: https://orcid.org/0000-0003-0240-0369)
- Zhifei Wang (ORCID: https://orcid.org/0000-0002-3197-4380)
- Hao Wu (ORCID: https://orcid.org/0000-0002-5379-855X)
Institutions
- Central South University (CN)
- Third Xiangya Hospital (CN)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-01-27
- DOI
- https://doi.org/10.1038/s41419-025-07347-z
- Citations
- 2
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.22
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Hunan Province