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NeuroMolecular Medicine

, Volume 16, Issue 1, pp 70–82 | Cite as

Role of Histone Lysine Methyltransferases SUV39H1 and SETDB1 in Gliomagenesis: Modulation of Cell Proliferation, Migration, and Colony Formation

  • Anastasia Spyropoulou
  • Antonios Gargalionis
  • Georgia Dalagiorgou
  • Christos Adamopoulos
  • Kostas A. Papavassiliou
  • Robert William Lea
  • Christina PiperiEmail author
  • Athanasios G. PapavassiliouEmail author
Original Paper

Abstract

Posttranslational modifications of histones are considered as critical regulators of gene expression, playing significant role in the pathogenesis and progression of tumors. Trimethylation of histone 3 lysine 9 (H3K9me3), a repressed transcription mark, is mainly regulated by the histone lysine N-methyltransferases (HKMTs), SUV39H1 and SETDB1. The present study investigated the implication of these HKMTs in glioma progression. SUV39H1 and SETDB1 expression was upregulated in glioma cell lines (GOS-3, 1321N1, T98G, U87MG) and in glioma tissues compared to normal brain being positively correlated with grade and histological malignancy. Suppression by siRNA of the two HKMTs for 24 and 48 h resulted in significantly reduced proliferation of GOS-3 and T98G glioma cells with siSUV39H1 effects been most prominent. Furthermore, HKMTs knockdown-induced apoptosis with a high rate of apoptotic cells have been observed after siSUV39H1 and siSETDB1 for both cell lines. Additionally, suppression of the two HKMTs reduced cell migration and clonogenic ability of both glioma cell lines. Our results indicate overexpression of SETDB1 and SUV39H1 in gliomas. Treatments that alter HKMT expression affect the proliferative and apoptotic rates in glioma cells as well as their migratory and colony formation capacity. These data suggest that both HKMTs and especially SUV39H1 may serve as novel biomarkers for future therapeutic targeting of these tumors.

Keywords

Gliomas Histone lysine methylation H3K9me3 SUV39H1 SETDB1 Tumorigenesis 

Abbreviations

BRAF

Serine/threonine-protein kinase B-raf

Dnmt

DNA (cytosine-5)-methyltransferase

DOT1L

Histone-lysine N-methyltransferase, H3 lysine-79 specific

EZH2

Enhancer of Zeste 2

G9A

Histone-lysine N-methyltransferase EHMT2

HCC

Hepatocellular carcinoma

HKDM

Histone lysine demethylase

HKMT

Histone lysine N-methyltransferase

HP1

Heterochromatin protein 1

IDH1

Isocitrate dehydrogenase 1

SET9

Histone-lysine N-methyltransferase SETD7

SETDB1

SET domain bifurcated 1

SMYD3

SET and MYND domain-containing protein 3

SUV39H1

Suppressor of variegation 3–9 homolog 1

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Anastasia Spyropoulou
    • 1
  • Antonios Gargalionis
    • 1
  • Georgia Dalagiorgou
    • 1
  • Christos Adamopoulos
    • 1
  • Kostas A. Papavassiliou
    • 1
  • Robert William Lea
    • 2
  • Christina Piperi
    • 1
    Email author
  • Athanasios G. Papavassiliou
    • 1
    Email author
  1. 1.Department of Biological Chemistry, Medical SchoolUniversity of AthensAthensGreece
  2. 2.Department of Biological SciencesUniversity of Central LancashirePrestonUK

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