PO.MCB09.04 · 分子与细胞生物学

线粒体生物发生为2级脑膜瘤的能量需求供能

Mitochondrial biogenesis fuels the energetic demands of grade 2 meningiomas

海报缩略图:线粒体生物发生为2级脑膜瘤的能量需求供能
编号 3287 展板 19 时间 4/20 02:00–05:00 区域 Section 23 主讲 Sueli Oba-Shinjo, PhD
分会场 Metabolic Studies in Brain, Pediatric, and Hematologic Cancers
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作者与单位 Authors & Affiliations

Stella G. Cavalcante1, Benedito J. A. Pereira1, Antonio M. Lerario2, Sueli M. Oba-Shinjo1, Suely Kazue Nagahashi Marie3

1Neurology, University of Sao Paulo, Faculty of Medicine, Sao Paulo, Brazil,2Internal Medicine, University of Michigan, Ann Arbor, MI,3University of São Paulo, São Paulo, Brazil

摘要 Abstract

中文摘要
脑膜瘤是最常见的原发性颅内肿瘤,占所有脑肿瘤的37.6%,主要被分类为1级(G1)或2级(G2)。虽然G1肿瘤通常呈良性临床病程,但G2脑膜瘤更具侵袭性并表现出更高的复发率。尽管具有临床相关性,G2脑膜瘤的代谢特征——尤其是线粒体功能的贡献——仍未得到充分明确。线粒体作为负责ATP产生的细胞动力工厂,对满足肿瘤生长升高的代谢需求至关重要。既往转录组学研究提示,G2脑膜瘤表现出增强的氧化代谢、细胞分裂和运动能力。本研究的目的是鉴定支持G2肿瘤能量需求的线粒体组分。转录组学分析显示,与G1脑膜瘤相比,G2中TFAM(线粒体DNA[mtDNA]的主调控因子和保护因子)的表达升高。其转录共激活因子PGC1-alpha(由PPARGC1A编码)也上调,且两个基因表现出强正相关,提示TFAM/PGC1-alpha轴可能驱动G2肿瘤中mtDNA拷贝数的增加。免疫染色证实了TFAM的分级特异性定位,G2肿瘤表现出更弥漫的胞质分布。此外,G2脑膜瘤表现出增强的线粒体活性,表现为线粒体核糖体基因表达上调以及氧化磷酸化和三羧酸循环通路的激活。总的来说,这些发现表明TFAM/PGC1-alpha/mtDNA轴在G2脑膜瘤中被激活,可能使得能够产生维持其增强的增殖和迁移能力所需的升高的能量。
查看英文原文 English abstract
Meningioma is the most common primary intracranial tumor, accounting for 37.6% of all brain tumors, and is predominantly classified as grade 1 (G1) or 2 (G2). While G1 tumors typically follow a benign clinical course, G2 meningiomas are more aggressive and exhibit higher recurrence rates. Despite their clinical relevance, the metabolic features of G2 meningiomas - particularly the contribution of mitochondrial function - remain poorly defined. Mitochondria, the cellular powerhouses responsible for ATP production, are essential for meeting the elevated metabolic demands of tumor growth. Prior transcriptomic studies suggest that G2 meningiomas exhibit enhanced oxidative metabolism, cell division, and motility. The objective of this study was to identify mitochondrial components that support the bioenergetic requirements of G2 tumors. Transcriptomic analysis revealed elevated expression of TFAM, the master regulator and protector of mitochondrial DNA (mtDNA), in G2 compared to G1 meningiomas. Its transcriptional coactivator PGC1-alpha (encoded by PPARGC1A ) was also upregulated, and both genes demonstrated a strong positive correlation, suggesting that the TFAM/PGC1-alpha axis may drive increased mtDNA copy number in G2 tumors. Immunostaining confirmed grade-specific TFAM localization, with G2 tumors displaying more diffuse cytosolic distribution. Furthermore, G2 meningiomas showed increased mitochondrial activity, evidenced by upregulated mitoribosomal gene expression and activation of oxidative phosphorylation and tricarboxylic acid cycle pathways. Collectively, these findings indicate that the TFAM/PGC1-alpha/mtDNA axis is activated in G2 meningiomas, potentially enabling the elevated energy production needed to sustain their increased proliferative and migratory capacity.
利益披露 Disclosure
S. G. Cavalcante, None.. B. J. A. Pereira, None.. A. M. Lerario, None.. S. M. Oba-Shinjo, None.

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