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

Autor: Mattia Russel Pantalone, Natalia Landázuri, Imran Nawaz, Belghis Davoudi, Tomas J. Ekström, Atosa Estekizadeh, Giuseppe Stragliotto, Afsar Rahbar, Li-Fu Hu
Rok vydání: 2019
Předmět:
Zdroj: Oncology Reports.
ISSN: 1791-2431
1021-335X
DOI: 10.3892/or.2019.7074
Popis: 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
Databáze: OpenAIRE