Hypoxia-induced USP22-BMI1 axis promotes the stemness and malignancy of glioma stem cells via regulation of HIF-1α

Life Sci. 2020 Apr 15:247:117438. doi: 10.1016/j.lfs.2020.117438. Epub 2020 Feb 15.

Abstract

Aims: This study intends to investigate the mechanisms of ubiqutin-specific protease 22 (USP22)/B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) on the biological phenotypes of glioma stem cells (GSCs) under hypoxia.

Main methods: Western blot, Cell Counting Kit-8, colony formation and flow cytometry assays were preformed to evaluate cells biological behaviors. Luciferase assay was utilized to identify the associations among USP22, HIF-1α and BMI1.

Key findings: Silencing USP22 reduced the stemness and proliferation of GSCs, and increased its apoptosis in response to hypoxia. Whilst, overexpression of BMI1 reversed these phenomena. Whilst, a significant decrease in proliferation and stemness of GSCs caused by HIF-1α exhaustion were inversed by overexpression of USP22 or BMI1.

Significance: Function of USP22-BMI1 on biological behaviors of GSCs was regulated by HIF-1α in response to hypoxia.

Keywords: Apoptosis; GSCs stemness; Hypoxia; Quiescence; Redox.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Glioma / therapy*
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism*
  • Signal Transduction
  • Tumor Hypoxia
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • BMI1 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Polycomb Repressive Complex 1
  • Ubiquitin Thiolesterase
  • Usp22 protein, human