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Human cytomegalovirus infection promotes the stemness of U251 glioma cells
Author(s) -
Wang Xinhui,
Hu Ming,
Xing Feifei,
Wang Mengyuan,
Wang Bin,
Qian Dongmeng
Publication year - 2017
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24708
Subject(s) - human cytomegalovirus , glioma , biology , gene silencing , downregulation and upregulation , cell growth , cell , virology , small interfering rna , transfection , stem cell , cell culture , cancer research , microbiology and biotechnology , virus , genetics , gene
Glioblastoma (GBM) are the most common and aggressive tumors of human brain. Recent studies showed that human cytomegalovirus (HCMV) can induce malignant transformation of tumor cells to maintain stemness. Transcription factor 5 (ATF5) is an anti‐apoptotic protein that is highly expressed in malignant glioma. The aim of this study is to investigate the effect of HCMV infection on the stem cell makers of U251 cells. U251 cells were infected by AD169 HCMV strain (MOI = 1). The expression of stem cell makers (CD133, NES, Notch1) in infected U251 cells were compared with the expression in uninfected U251 cell to see the difference between them. Then, the changes of cell proliferation activity and the expression level of Notch intracellular domain (NICD), Notch1, ATF5, and IE protein were detected in the infected cells, and the expressions of Notch1 and NICD were increased. Cell proliferation assay showed that HCMV infection significantly increased the proliferation. These cells could form tumor spheres in non‐adherent conditions. Consistent with these findings, the effect of silencing ATF5 on the proliferation of HCMV‐infected U251 cells was also examined. The result shows that short interfering RNA‐mediated ATF5 downregulation inhibited this process. These findings imply that HCMV infection may regulate ATF5 signaling pathway to increase cell malignant traits and maintain stemness. J. Med. Virol. 89:878–886, 2017 . © 2016 Wiley Periodicals, Inc.