Luo Kui, Zhuang Kai, Wu Hao, Chen Yuanbing, Liu Yi, Yang Fan, Wang Zhifei
Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Cell Death Dis. 2025 Jan 27;16(1):48. doi: 10.1038/s41419-025-07347-z.
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.
胶质瘤是一种常见的具有破坏性的脑肿瘤,高度异质性且预后较差。开发诊断和预后标志物以早期识别和治疗胶质瘤将显著改善治疗效果。在此,我们对33个胶质瘤样本和15个正常脑样本进行了RNA下一代测序。我们发现脂滴包被蛋白1(PLIN1)在胶质瘤中下调且与较差的预后相关。随后的实验表明,PLIN1的上调导致胶质瘤细胞生长和侵袭受到抑制。此外,PLIN1的过表达增加了胶质瘤细胞中的脂质积累,脂质生物合成相关基因的表达增加,脂解相关基因的表达减少。从机制上讲,我们揭示了PI3K/AKT轴可调节胶质瘤中PLIN1的水平,抑制PI3K/AKT轴的活性可增加胶质瘤中PLIN1的水平。总之,PI3K/AKT轴失调导致PLIN1下调以及随后胶质瘤中的肿瘤增殖、侵袭和脂质代谢重编程。