RGD Reference Report - Role of histone lysine methyltransferases SUV39H1 and SETDB1 in gliomagenesis: modulation of cell proliferation, migration, and colony formation. - Rat Genome Database

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Role of histone lysine methyltransferases SUV39H1 and SETDB1 in gliomagenesis: modulation of cell proliferation, migration, and colony formation.

Authors: Spyropoulou, A  Gargalionis, A  Dalagiorgou, G  Adamopoulos, C  Papavassiliou, KA  Lea, RW  Piperi, C  Papavassiliou, AG 
Citation: Spyropoulou A, etal., Neuromolecular Med. 2014 Mar;16(1):70-82. doi: 10.1007/s12017-013-8254-x. Epub 2013 Aug 13.
RGD ID: 9590166
Pubmed: PMID:23943221   (View Abstract at PubMed)
DOI: DOI:10.1007/s12017-013-8254-x   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SETDB1Humanhigh grade glioma severityIEP protein:increased expression:brain and cell nucleus (human)RGD 
Setdb1Rathigh grade glioma severityISOSETDB1 (Homo sapiens)protein:increased expression:brain and cell nucleus (human)RGD 
Setdb1Mousehigh grade glioma severityISOSETDB1 (Homo sapiens)protein:increased expression:brain and cell nucleus (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Setdb1  (SET domain bifurcated histone lysine methyltransferase 1)

Genes (Mus musculus)
Setdb1  (SET domain, bifurcated 1)

Genes (Homo sapiens)
SETDB1  (SET domain bifurcated histone lysine methyltransferase 1)


Additional Information