Expression and functional implications of USP17 in glioma

Neurosci Lett. 2016 Mar 11:616:125-31. doi: 10.1016/j.neulet.2016.01.015. Epub 2016 Jan 14.

Abstract

Glioma is the most common and malignant brain tumor with extremely poor prognosis. It is crucial to understand the molecular characteristics of glioma and find out more effective therapeutic targets for the treatment of glioma. USP17 is a novel deubiquitinating enzyme that is differentially expressed in certain types of solid tumor. Our present study investigated the pathological functions and clinical significance of USP17 in glioma for the first time. We found that USP17 was down-regulated in glioma tissue compared with normal tissues. Overexpression of USP17 in glioma cells reduced their tumorigenesis and proliferation ability through reducing Ras and Myc protein levels. Subsequent in vivo experiments showed that overexpression of USP17 suppressed tumor progression in an orthotopic glioma models. Further, study of a cohort of 104 patients with stage I-IV glioma showed that USP17 expression was negatively associated with the WHO grade (p<0.001). USP17 was more highly expressed in low grade (I+II) glioma than high-grade (III+IV) glioma (p<0.001). Taken together, our results indicate that USP17 might play important functions in glioma through suppressing glioma tumorigenesis and proliferation.

Keywords: Glioma; Proliferation; Stage; Tumorigenesis; USP17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / pathology
  • Cell Proliferation
  • Down-Regulation
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Female
  • Glioma / enzymology*
  • Glioma / pathology
  • Humans
  • Male
  • Mice, Nude
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Transplantation

Substances

  • Endopeptidases
  • USP17L2 protein, human