PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway

Yizheng Wang; Shiyang Zhang; Zijun Zhao; Qianxu Jin; Zairan Wang; Zihan Song; Liqiang Liu; Zongmao Zhao

doi:10.1016/j.imbio.2024.152802

PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway

Immunobiology. 2024 Mar 30;229(3):152802. doi: 10.1016/j.imbio.2024.152802. Online ahead of print.

Authors

Yizheng Wang¹, Shiyang Zhang², Zijun Zhao³, Qianxu Jin⁴, Zairan Wang⁵, Zihan Song², Liqiang Liu⁶, Zongmao Zhao⁷

Affiliations

¹ Pain Rehabilitation, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
² Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
³ Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing 100000, China.
⁴ Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
⁵ Department of Neurosurgery, Peking Union Medical College Hospital, Beijing 100000, China.
⁶ Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. Electronic address: llq74@sina.com.
⁷ Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China. Electronic address: zzm692017@sina.com.

PMID: 38569452
DOI: 10.1016/j.imbio.2024.152802

Abstract

Background: Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated.

Methods: This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored.

Results: Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway.

Conclusions: PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.

Keywords: Glioma; Immune cell homeostasis; PI3K/AKT/mTOR pathway; PSMC2; Prognosis.