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Epigenetic silencing and activation of transcription: influence on the radiation sensitivity of glioma cell lines.
Sak, Ali; Kübler, Dennis; Bannik, Kristina; Groneberg, Michael; Strunz, Sonja; Kriehuber, Ralf; Stuschke, Martin.
Afiliación
  • Sak A; a Department of Radiotherapy , University Hospital Essen , Essen , Germany.
  • Kübler D; a Department of Radiotherapy , University Hospital Essen , Essen , Germany.
  • Bannik K; a Department of Radiotherapy , University Hospital Essen , Essen , Germany.
  • Groneberg M; a Department of Radiotherapy , University Hospital Essen , Essen , Germany.
  • Strunz S; b Department of Biomathematics and Bioinformatics , Institute of Genetics and Biometry, Leibniz-Institute for Farm Animal Biology , Dummerstorf , Germany.
  • Kriehuber R; c Department of Safety and Radiation Protection , Forschungszentrum Jülich GmbH , Jülich , Germany.
  • Stuschke M; a Department of Radiotherapy , University Hospital Essen , Essen , Germany.
Int J Radiat Biol ; 93(5): 494-506, 2017 05.
Article en En | MEDLINE | ID: mdl-28044469
ABSTRACT

PURPOSE:

To uncover the role of EZH2 and its opponent ASHL2, a polycomb and trithorax group protein, respectively, on the radioresponsiveness of glioma cell lines. MATERIALS AND

METHODS:

Expression of EZH2 and ASHL2 was inhibited by siRNA in glioma cell lines. The effect on histone methylation, gene expression, DNA damage repair signaling, cell cycle checkpoints, apoptosis and tumor control were evaluated.

RESULTS:

Inhibition of EZH2 (EZH2i) led to a transcriptional dysregulation with upregulation of 544 and downregulation of 445 genes. In comparison, ASH2L inhibition (ASH2Li) had an opposed effect with upregulation of 289 and downregulation of 970 genes. EZH2i and ASH2Li significantly reduced methylation of H3K27 and increased methylation of H3K9, respectively. EZH2i and ASH2Li significantly increased and decreased the number of residual γH2AX foci at 24 h after IR, respectively. The former significantly increased radiation-induced cell cycle arrest in G2/M and apoptotic cell death, while ASH2Li decreased both. In addition, a significant shift of the radioresponse curve by -1.22 + 0.23 Gy (p < 0.0001) in the plaque monolayer assay was found after EZH2i in A7 but not in M059K.

CONCLUSION:

Overall, epigenetic modulation is a promising approach to evaluate the role of chromatin structure for the radioresponsiveness of glioma cell lines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_brain_nervous_system_cancer Asunto principal: Tolerancia a Radiación / Factores de Transcripción / Proteínas Nucleares / Activación Transcripcional / Epigénesis Genética / Proteínas de Unión al ADN / Proteína Potenciadora del Homólogo Zeste 2 / Glioma Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Radiat Biol Asunto de la revista: RADIOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_brain_nervous_system_cancer Asunto principal: Tolerancia a Radiación / Factores de Transcripción / Proteínas Nucleares / Activación Transcripcional / Epigénesis Genética / Proteínas de Unión al ADN / Proteína Potenciadora del Homólogo Zeste 2 / Glioma Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Radiat Biol Asunto de la revista: RADIOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania
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