SH3BGRL3, transcribed by STAT3, facilitates glioblastoma tumorigenesis by activating STAT3 signaling

Biochem Biophys Res Commun. 2021 Jun 4:556:114-120. doi: 10.1016/j.bbrc.2021.03.165. Epub 2021 Apr 8.

Abstract

Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.

Keywords: GSCs; Glioblastoma; SH3BGRL3; STAT3; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Carcinogenesis* / genetics
  • Carcinogenesis* / metabolism
  • Carcinogenesis* / pathology
  • Cell Proliferation
  • Cell Self Renewal
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Prognosis
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Transcription, Genetic*

Substances

  • Adaptor Proteins, Signal Transducing
  • SH3BGRL3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human