Acute hypoxia induces upregulation of microRNA-210 expression in glioblastoma spheroids

CNS Oncol. 2015;4(1):25-35. doi: 10.2217/cns.14.48.

Abstract

Aim: Tumor hypoxia and presence of tumor stem cells are related to therapeutic resistance and tumorigenicity in glioblastomas. The aim of the present study was therefore to identify microRNAs deregulated in acute hypoxia and to identify possible associated changes in stem cell markers.

Materials & methods: Glioblastoma spheroid cultures were grown in either 2 or 21% oxygen. Subsequently, miRNA profiling was performed and expression of ten stem cell markers was examined.

Results: MiRNA-210 was significantly upregulated in hypoxia in patient-derived spheroids. The stem cell markers displayed a complex regulatory pattern.

Conclusion: MiRNA-210 appears to be upregulated in hypoxia in immature glioblastoma cells. This miRNA may represent a therapeutic target although it is not clear from the results whether this miRNA may be related to specific cancer stem cell functions.

Keywords: cancer stem cell; glioblastoma; hypoxia; microRNA; profiling; spheroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Spheroids, Cellular
  • Time Factors
  • Up-Regulation / physiology*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN210 microRNA, human
  • MicroRNAs