Caveolin-1 promotes glioma progression and maintains its mitochondrial inhibition resistance

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

doi:10.1007/s12672-023-00765-5

Caveolin-1 promotes glioma progression and maintains its mitochondrial inhibition resistance

Discov Oncol. 2023 Aug 29;14(1):161. doi: 10.1007/s12672-023-00765-5.

Authors

Yu'e Liu^#¹, Yi Chen^#², Fei Wang^#³, Jianghua Lin¹, Xiao Tan⁴, Chao Chen⁵, Lei-Lei Wu⁶, Xiaoling Zhang^{7

8}, Yi Wang⁹, Yufeng Shi^{4

10}, Xiaoli Yan¹¹, Kaijun Zhao¹²

Affiliations

¹ Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
² The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China.
³ Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai, 201399, China.
⁴ Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, 200092, China.
⁵ Department of Neurosurgery, Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China.
⁶ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
⁷ National Joint Engineering Laboratory for Human Disease Animal Models, First Affiliated Hospital of Jilin University, Changchun, China.
⁸ Key Laboratory of Organ Regeneration and Transplantation, First Hospital of Jilin University, Changchun, China.
⁹ Department of Critical Care Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
¹⁰ Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, 200092, China.
¹¹ Laboratory of Immunology and Pathogen Biology, School of Medicine, Tongji University, Shanghai, 200092, China. yanxl72@tongji.edu.cn.
¹² Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China. zkjwcfzwh@163.com.

^# Contributed equally.

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.

Keywords: CAV1; DNA methylation; Drug resistance; Glioma; Immunotherapy.

Abstract

Grants and funding