Gene knockdown of CENPA reduces sphere forming ability and stemness of glioblastoma initiating cells

Jinan Behnan, Zanina Grieg, Mrinal Joel, Ingunn Ramsness, Biljana Stangeland

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

CENPA is a centromere-associated variant of histone H3 implicated in numerous malignancies. However, the role of this protein in glioblastoma (GBM) has not been demonstrated. GBM is one of the most aggressive human cancers. GBM initiating cells (GICs), contained within these tumors are deemed to convey characteristics such as invasiveness and resistance to therapy. Therefore, there is a strong rationale for targeting these cells. We investigated the expression of CENPA and other centromeric proteins (CENPs) in GICs, GBM and variety of other cell types and tissues. Bioinformatics analysis identified the gene signature: high_CENP(AEFNM)/low_CENP(BCTQ) whose expression correlated with significantly worse GBM patient survival. Knockdown of CENPA reduced sphere forming ability, proliferation and cell viability of GICs. We also detected significant reduction in the expression of stemness marker SOX2 and the proliferation marker Ki67. These results indicate that CENPA might represent a promising therapeutic target for GBM treatment.

Original languageEnglish (US)
Pages (from-to)6-18
Number of pages13
JournalNeuroepigenetics
Volume7
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • Brain tumor
  • CENPA
  • Centromeric proteins
  • GBM
  • Glioblastoma
  • Glioblastoma initiating cells and therapeutic targeting

ASJC Scopus subject areas

  • Biochemistry
  • Developmental Neuroscience
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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