2. Academic Validation
  3. PVT1 promotes proliferation and macrophage immunosuppressive polarization through STAT1 and CX3CL1 regulation in glioblastoma multiforme

PVT1 promotes proliferation and macrophage immunosuppressive polarization through STAT1 and CX3CL1 regulation in glioblastoma multiforme

  • CNS Neurosci Ther. 2024 Jan;30(1):e14566. doi: 10.1111/cns.14566.
Lijie Huang 1,  Zheng Wang 2,  Chihyi Liao 3,  Zheng Zhao 3,  Hua Gao 4,  Ruoyu Huang 2,  Jing Chen 3,  Fan Wu 3,  Fan Zeng 3,  Ying Zhang 3,  Tao Jiang 2 3 5 6 7,  Huimin Hu 3
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Beijing Neurosurgical Institute, Capital Medical University, China.
  • 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 3 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • 4 Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
  • 5 Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.
  • 6 China National Clinical Research Center for Neurological Diseases, Beijing, China.
  • 7 Chinese Glioma Genome Atlas Network and Asian Glioma Genome Atlas Network, Beijing, China.
PMID: 38287522 DOI: 10.1111/cns.14566
Abstract

Aims: This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA, in glioblastoma multiforme (GBM) and its impact on the tumor microenvironment (TME).

Methods: We assessed aberrant PVT1 expression in glioma tissues and its impact on GBM cell growth in vitro and in vivo. Additionally, we investigated PVT1's role in influencing glioma-associated macrophages. To understand PVT1's role in cell growth and the immunosuppressive TME, we performed a series of comprehensive experiments.

Results: PVT1 was overexpressed in GBM due to copy number amplification, correlating with poor prognosis. Elevated PVT1 promoted GBM cell proliferation, while its downregulation inhibited growth in vitro and in vivo. PVT1 inhibited type I interferon-stimulated genes (ISGs), with STAT1 as the central hub. PVT1 correlated with macrophage enrichment and regulated CX3CL1 expression, promoting recruitment and M2 phenotype polarization of macrophages. PVT1 localized to the cell nucleus and bound to DHX9, enriching at the promoter regions of STAT1 and CX3CL1, modulating ISGs and CX3CL1 expression.

Conclusion: PVT1 plays a significant role in GBM, correlating with poor prognosis, promoting cell growth, and shaping an immunosuppressive TME via STAT1 and CX3CL1 regulation. Targeting PVT1 may hold therapeutic promise for GBM patients.

Keywords

CX3CL1; DHX9; PVT1; interferon-stimulated genes; macrophages.

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