@article{TCR26137,
author = {Wenqing Jiang and Lingyun Li and Huamin Tang and Bin Gu and Dongju Feng and Feng Zhou and Yingxia Liu and Xianyi Xu and Yun Chen and Kun Yao and Weixing Hu},
title = {Human herpesvirus 6 U94 suppresses tumor cell proliferation and invasion by inhibiting Akt/GSK3β signaling in glioma},
journal = {Translational Cancer Research},
volume = {7},
number = {6},
year = {2018},
keywords = {},
abstract = {Background: Glioma is a highly malignant brain tumor with limited therapeutic options. We reported previously that the DNA and protein of human herpesvirus 6 (HHV-6) could be detected in glioma tumor tissues. However, the effects of HHV-6 U94, which is abundantly expressed during the virus’ latency period, on glioma progression remain unknown. In the present study, we aimed to determine on the roles of HHV-6 U94 in glioma progression.
Methods: The ectopic expression of U94 in glioma U87 cells was achieved using lentivirus infection. The effects of HHV-6 U94 on cell proliferation, migration, and invasion were examined using cell counting kit-8 (CCK-8), colony formation, wound healing, Transwell migration, and invasion assays. The gene expression profiles of U94-expressing U87 cells were analyzed using microarray analysis and confirmed by quantitative RT-PCR and western blotting analysis. The effects of HHV-6 U94 on glioma tumor growth were evaluated using a xenograft nude mouse model.
Results: We found that ectopic expression of U94 in glioma U87 cells dramatically inhibited colony formation and cell proliferation in vitro, and suppressed xenograft tumorigenesis in glioma-bearing nude mice. In addition, overexpression of U94 suppressed the migration and invasion of glioma U87 cells. Furthermore, enhanced expression of U94 in glioma cells downregulated ras-related protein rap-1A (RAP1A), solute carrier family 7 member 11 (SLC7A11), forkhead box P1 (FOXP1), and transcription factor 4 (TCF4) expression by inhibiting Akt kinase (AKT/glycogen synthase kinase 3 beta (GSK3β) signaling, which proteins are associated with the malignant phenotypes of glioma cells.
Conclusions: Taken together, these data indicated that HHV-6 U94 could suppress tumor cell proliferation and invasion by inhibiting AKT/GSK3β signaling in glioma.},
issn = {2219-6803}, url = {https://tcr.amegroups.org/article/view/26137}
}