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

Metab Brain Dis. 2024 Jun;39(5):895-907. doi: 10.1007/s11011-024-01345-4. Epub 2024 May 21.

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.

Keywords: EIF4A3; Immune escape; Meningiomas; PD-L1; hsa_circ_0004872.

MeSH terms

  • Apoptosis
  • B7-H1 Antigen* / genetics
  • B7-H1 Antigen* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • DEAD-box RNA Helicases
  • Eukaryotic Initiation Factor-4A* / genetics
  • Eukaryotic Initiation Factor-4A* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Meningeal Neoplasms* / genetics
  • Meningeal Neoplasms* / immunology
  • Meningeal Neoplasms* / metabolism
  • Meningeal Neoplasms* / pathology
  • Meningioma* / genetics
  • Meningioma* / immunology
  • Meningioma* / metabolism
  • Meningioma* / pathology
  • RNA, Circular* / genetics
  • Tumor Escape

Substances

  • B7-H1 Antigen
  • RNA, Circular
  • CD274 protein, human
  • Eukaryotic Initiation Factor-4A
  • EIF4A3 protein, human
  • DEAD-box RNA Helicases