蛋白质洞穴蛋白1促进胶质瘤进展并维持其对线粒体抑制的抵抗性。
Caveolin-1 promotes glioma progression and maintains its mitochondrial inhibition resistance.
发表日期:2023 Aug 29
作者:
Yu'e Liu, Yi Chen, Fei Wang, Jianghua Lin, Xiao Tan, Chao Chen, Lei-Lei Wu, Xiaoling Zhang, Yi Wang, Yufeng Shi, Xiaoli Yan, Kaijun Zhao
来源:
Brain Structure & Function
摘要:
胶质瘤是致命的脑癌,缺乏有效的治疗方法。挑战包括缺乏有效的治疗靶点,肿瘤内和肿瘤间的异质性,缺乏有效药物以及免疫抑制的微环境等。破译胶质瘤的发病机制并找出其作用机制对于胶质瘤治疗是迫切和必要的。鉴定预后生物标志物并靶向生物标志物基因将成为一种有前景的治疗方法。根据我们的RNA测序数据,我们发现氧化磷酸化(OXPHOS)抑制敏感和OXPHOS抵抗细胞系中,支架蛋白CAV1在抵抗组中高度表达,而在敏感组中则没有表达。通过对我们的RNA测序数据、全基因组亚硫酸盐测序(WGBS)数据和公共数据库的综合分析,我们发现CAV1在胶质瘤中高表达,并且其表达与病理过程呈正相关,较高的CAV1表达预示着较短的总生存期。进一步分析表明:(1)CAV1高表达组的差异化基因富集于免疫浸润和免疫反应;(2)CAV1与肿瘤转移标志物呈正相关;(3)胶质瘤组中CAV1启动子的甲基化水平在较高分期中较低;(4)CAV1与胶质瘤干细胞相关;(5)较高的CAV1表达使胶质瘤细胞对氧化磷酸化抑制剂具有抵抗性。因此,我们确定了一个关键基因CAV1,并解析了其在胶质瘤进展和预后中的作用,提出CAV1可能是胶质瘤的治疗靶点。
© 2023. Springer Science+Business Media, LLC.
Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy.From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival.Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells' resistant to oxidative phosphorylation inhibitors.Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas.© 2023. Springer Science+Business Media, LLC.