Caveolin-1 Promotes Glioma Progression and Maintains Its Mitochondrial Inhibition Resistance

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2023 Aug 29

PMID 37642765

Authors

Yue Liu

Yi Chen

Fei Wang

Jianghua Lin

Xiao Tan

Chao Chen

Lei-Lei Wu

Xiaoling Zhang

Yi Wang

Yufeng Shi

Xiaoli Yan

Kaijun Zhao

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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