RANBP10 promotes glioblastoma progression by regulating the FBXW7/c-Myc pathway

Cell Death Dis. 2021 Oct 20;12(11):967. doi: 10.1038/s41419-021-04207-4.

Abstract

RAN binding protein 10 (RANBP10), a ubiquitously expressed and evolutionarily conserved protein, as a RAN-GTP exchange factor (GEF) to regulate several factors involved in cellular progression. Previous studies showed that RANBP10 was overexpressed in prostate cancer cells and was responsible for androgen receptor (AR) activation. However, the biological function of RANBP10 in glioblastoma (GBM) has not been studied. Here, we found that RANBP10 was overexpressed in GBM, and high RANBP10 expression was closely linked to poor survival of patients with GBM. Downregulation of RANBP10 significantly inhibited cell proliferation, migration, invasion, and tumor growth of GBM cells. In addition, we revealed that RANBP10 could suppress the promoter activity of FBXW7, and thereby increase the protein stability of c-Myc in GBM cells. Silencing of FBXW7 in RANBP10-knockdown GBM cells could partly negate the effects induced by RANBP10 downregulation. Taken together, our findings established that RANBP10 significantly promoted GBM progression by control of the FBXW7-c-Myc axis, and suggest that RANBP10 may be a potential target in GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • F-Box-WD Repeat-Containing Protein 7 / genetics*
  • F-Box-WD Repeat-Containing Protein 7 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Glioblastoma / pathology*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Microtubule-Associated Proteins / metabolism*
  • Models, Biological
  • Neoplasm Invasiveness
  • Prognosis
  • Protein Stability
  • Proteolysis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction*
  • Transcription, Genetic
  • Tumor Stem Cell Assay
  • Ubiquitination

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Guanine Nucleotide Exchange Factors
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-myc
  • RANBP10 protein, human