SH3BGRL2 functions as a crucial tumor suppressor in glioblastoma tumorigenesis

Biochem Biophys Res Commun. 2021 Apr 2:547:148-154. doi: 10.1016/j.bbrc.2021.02.035. Epub 2021 Feb 19.

Abstract

Glioblastoma is the most common and severe primary intrinsic tumor of the central nervous system. Glioblastoma harbors glioma stem cells (GSCs) as it not only possesses self-renewal and differentiation properties but also accounts for significant chemotherapy resistance and recurrence. Thus, targeting GSCs may be essential in overcoming the resistance and recurrence thereby improving GBM treatment. However, the underlying mechanism to sustain GSCs remains largely unknown. Here, we report that SH3 domain binding glutamate-rich protein like 2 (SH3BGRL2) is weakly expressed in glioblastoma multiforme (GBM) and isocitrate dehydrogenase1 (IDH1) wildtype GBM and correlated with glioma patients' poor prognosis. Moreover, ectopic expression of SH3BGRL2 significantly inhibited GBM cell growth, migration, and GSCs self-renewal in vitro as well as tumor growth in vivo. Additionally, we found that SH3BGRL2 suppressed SOX2 and CD133 expression, which are key regulators involved in GSCs self-renewal. Collectively, our findings shed additional light on SH3BGRL2 has potential to serve as a biomarker and a potent therapeutic target for patients with glioma.

Keywords: Biomarker; GSCs; Glioma; SH3BGRL2; Tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cell Self Renewal
  • Computational Biology / methods
  • Genes, Tumor Suppressor*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Staging
  • Survival Rate
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • SH3BGRL2 protein, human