The Immunomodulatory Effects of Vitamin D on COVID-19 Induced Glioblastoma Recurrence via the PI3K-AKT Signaling Pathway

Int J Mol Sci. 2024 Dec 2;25(23):12952. doi: 10.3390/ijms252312952.

Abstract

Glioma is a highly invasive brain cancer that is difficult to treat due to its complex molecular characteristics and poor prognosis. The COVID-19 pandemic has introduced additional clinical challenges for cancer patients, especially those with glioma. This study explored the molecular interactions between glioma and COVID-19 using integrated bioinformatics methods, including enrichment analysis, survival analysis, and molecular docking, focusing on the PI3K-Akt signaling pathway and the immunomodulatory role of vitamin D. From gene expression data of glioma and COVID-19, 203 common differentially expressed genes were identified, and six prognostic key genes-MYBL2, RBM6, VEPH1, AHNAK2, GNG10, and DUSP14-were further determined. After intersecting with vitamin D targets five prognostic key genes were determined-MYBL2, RBM6, VEPH1, AHNAK2 and GNG10. These genes play significant roles in the PI3K-Akt pathway and potentially interact with vitamin D. Molecular docking and single-cell RNA sequencing analyses suggest that vitamin D may improve the prognosis of glioma patients infected with COVID-19 by regulating these key genes and the PI3K-Akt pathway. The findings reveal molecular links between glioma and COVID-19, thereby providing new insights for developing targeted therapeutic strategies.

Keywords: COVID-19 induced glioblastoma recurrence; PI3K-AKT signaling pathway; pharmacology network; vitamin D.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • COVID-19* / immunology
  • COVID-19* / virology
  • Computational Biology / methods
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Humans
  • Molecular Docking Simulation*
  • Neoplasm Recurrence, Local
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • SARS-CoV-2
  • Signal Transduction*
  • Vitamin D* / metabolism
  • Vitamin D* / pharmacology
  • Vitamin D* / therapeutic use

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Vitamin D