VAV3 regulates glioblastoma cell proliferation, migration, invasion and cancer stem‑like cell self‑renewal

Mol Med Rep. 2023 Apr;27(4):94. doi: 10.3892/mmr.2023.12981. Epub 2023 Mar 24.

Abstract

Glioblastoma multiforme (GBM; World Health Organization grade IV) is one of the most common and aggressive malignant brain tumors and has no effective treatment. Therefore, elucidation of the molecular mechanism of glioma development is very important for finding new therapeutic strategies. The present study evaluated the expression level of Vav guanine nucleotide exchange factor 3 (VAV3) using bioinformatics analysis and demonstrated that VAV3 was overexpressed in human glioblastoma and associated with patient survival. Knock down of VAV3 using shRNA in glioblastoma cells significantly inhibited glioblastoma cell migration, invasion and proliferation. Furthermore, downregulation of VAV3 expression inhibited the stem cell self‑renewal capacity and decreased the expression levels of the stem cell markers Nestin and Sox2. Bioinformatic analysis demonstrated that VAV3 was a target gene of miR‑218. Furthermore, overexpression of VAV3 markedly reversed the tumor suppressor effect of miR‑218 in glioblastoma cell. These findings suggested that VAV3 could be a potential biomarker and therapeutic target for glioblastoma.

Keywords: Vav guanine nucleotide exchange factor 3; glioblastoma multiforme; miR‑218; proliferation; stemness.

MeSH terms

  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Self Renewal / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / pathology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / therapeutic use
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / metabolism

Substances

  • Proto-Oncogene Proteins c-vav
  • MicroRNAs
  • VAV3 protein, human
  • MIRN218 microRNA, human

Grants and funding

The present study was supported by The Natural Science Basic Research Plan in Shaanxi Province of China (grant no. 2021SF-273), Scientific Research Program Funded by Shaanxi Provincial Education Department (grant no. 20JG029) and Shaanxi Province Innovation capability support plan project (grant no. 2023-CX-PT-03).