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Hsa_circ_0004872 mitigates proliferation, metastasis and immune escape of meningioma cells by suppressing PD-L1.

Authors :
Chen, Kuo
Huang, Zhengming
Liu, Changsheng
Ouyang, Qian
Yan, Qing
Zheng, Wei
Huang, Yongkai
Source :
Metabolic Brain Disease. Jun2024, Vol. 39 Issue 5, p895-907. 13p.
Publication Year :
2024

Abstract

Meningioma is a prevalent intracranial malignancy known for its aggressive growth. Circular RNAs (circRNAs) play a crucial role in the development of various cancers. However, their involvement in meningioma remains understudied. This study aimed to investigate the function and underlying mechanism of hsa_circ_0004872 in meningioma. The molecular expression of hsa_circ_0004872, PD-L1 and EIF4A3 was identified by RT-qPCR and/or western blot assays. Cell viability, migration, and invasion were assessed through CCK-8 and Transwell assays, respectively. Cytotoxicity was determined using an LDH assay, and cell apoptosis was monitored by flow cytometry. The RNA and protein interactions were assessed through RNA-protein immunoprecipitation (RIP) and RNA pull down analyses. Our findings revealed that hsa_circ_0004872 expression was significantly downregulated in both meningioma tissue samples and cells. Overexpression of hsa_circ_0004872 inhibited the proliferation, metastasis, and immune escape of meningioma cells, as well as enhanced the cytotoxicity of CD8+ T cells by suppressing PD-L1. Furthermore, hsa_circ_0004872 directly interacted with EIF4A3, leading to the degradation of PD-L1 mRNA. Finally, inhibiting EIF4A3 improved the proliferation, metastasis, and immune escape of meningioma cells, as well as the cytotoxicity of CD8+ T cells. Our study demonstrated that hsa_circ_0004872 mitigated the proliferation, metastasis,and immune escape of meningioma cells by targeting the EIF4A3/PD-L1 axis. These findings suggested that hsa_circ_0004872 and EIF4A3 might serve as promising biological markers and therapeutic targets for meningioma treatment. Highlights: Hsa_circ_0004872 was downregulated in meningiomas and negatively correlated with PD-L1. Overexpression of hsa_circ_0004872 hindered the metastasis and immune escape of meningioma cells. Hsa_circ_0004872 competitively interacted to EIF4A3 to decay PD-L1 mRNA. EIF4A3 upregulation facilitated the metastasis and immune escape of meningioma cells. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08857490
Volume :
39
Issue :
5
Database :
Academic Search Index
Journal :
Metabolic Brain Disease
Publication Type :
Academic Journal
Accession number :
178339105
Full Text :
https://doi.org/10.1007/s11011-024-01345-4