5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells

  • Authors:
    • Atosa Estekizadeh
    • Natalia Landázuri
    • Mattia Russel Pantalone
    • Belghis Davoudi
    • Li‑Fu Hu
    • Imran Nawaz
    • Giuseppe Stragliotto
    • Tomas J. Ekström
    • Afsar Rahbar
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  • Published online on: March 18, 2019     https://doi.org/10.3892/or.2019.7074
  • Pages: 2927-2936
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Abstract

Glioblastoma (GBM) is the most aggressive form of brain tumor in adults, with a devastating outcome. Emerging evidence shows that human cytomegalovirus (HCMV) proteins and nucleic acids are present in GBM tissues. DNA methylation is important for the initiation and progression of cancer and is an established host response against invading nucleic acids. The expression and localization of DNA methyltransferase 1 (DNMT‑1) was assessed, and the effects of DNA methylation inhibitor 5‑azacytidine (5AZA) were analyzed in the context of the viral replication, proliferation and invasion capacities of HCMV‑infected GBM U343MG cells. In addition, the expression of various HCMV proteins and DNMT‑1 was examined in GBM tissue specimens obtained from five patients. DNMT‑1 was localized in the nucleus of cells expressing HCMV‑immediate early, whereas in cells expressing HCMV‑glycoprotein gB (gB), extranuclear/cytoplasmic localization was observed. This was also observed in vitro in U343MG cells. In addition, DNMT‑1 was localized to the extranuclear/cytoplasmic space of cells lining blood vessel walls within the GBM tumors. Treatment of infected U343MG cells with 5AZA did not affect viral replication, but reduced cell invasion and proliferation (P=0.05 and P<0.0001, respectively). However, 5AZA treatment of uninfected cells did not affect cell invasion (P=0.09), but proliferation was significantly reduced (P<0.0001). These findings may be of importance in further investigations aimed at using DNA methylation and viral inhibitors in GBM therapy.
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May-2019
Volume 41 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Estekizadeh A, Landázuri N, Pantalone MR, Davoudi B, Hu LF, Nawaz I, Stragliotto G, Ekström TJ and Rahbar A: 5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells. Oncol Rep 41: 2927-2936, 2019
APA
Estekizadeh, A., Landázuri, N., Pantalone, M.R., Davoudi, B., Hu, L., Nawaz, I. ... Rahbar, A. (2019). 5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells. Oncology Reports, 41, 2927-2936. https://doi.org/10.3892/or.2019.7074
MLA
Estekizadeh, A., Landázuri, N., Pantalone, M. R., Davoudi, B., Hu, L., Nawaz, I., Stragliotto, G., Ekström, T. J., Rahbar, A."5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells". Oncology Reports 41.5 (2019): 2927-2936.
Chicago
Estekizadeh, A., Landázuri, N., Pantalone, M. R., Davoudi, B., Hu, L., Nawaz, I., Stragliotto, G., Ekström, T. J., Rahbar, A."5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells". Oncology Reports 41, no. 5 (2019): 2927-2936. https://doi.org/10.3892/or.2019.7074