Amy Hansen
KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming
Hansen, Amy; Henderson, Stephen; Lagos, Dimitrios; Nikitenko, Leonid; Coulter, Eve; Roberts, Sinead; Gratrix, Fiona; Plaisance, Karlie; Renne, Rolf; Bower, Mark; Kellam, Paul; Boshoff, Chris
Authors
Stephen Henderson
Dimitrios Lagos
Dr Leonid Nikitenko L.Nikitenko@hull.ac.uk
Lecturer in Biomedical Sciences
Eve Coulter
Sinead Roberts
Fiona Gratrix
Karlie Plaisance
Rolf Renne
Mark Bower
Paul Kellam
Chris Boshoff
Abstract
Kaposi sarcoma herpesvirus (KSHV) induces transcriptional reprogramming of endothelial cells. In particular, KSHV-infected lymphatic endothelial cells (LECs) show an up-regulation of genes associated with blood vessel endothelial cells (BECs). Consequently, KSHV-infected tumor cells in Kaposi sarcoma are poorly differentiated endothelial cells, expressing markers of both LECs and BECs. MicroRNAs (miRNAs) are short noncoding RNA molecules that act post-transcriptionally to negatively regulate gene expression. Here we validate expression of the KSHV-encoded miRNAs in Kaposi sarcoma lesions and demonstrate that these miRNAs contribute to viralinduced reprogramming by silencing the cellular transcription factor MAF (musculoaponeurotic fibrosarcoma oncogene homolog). MAF is expressed in LECs but not in BECs. We identify a novel role for MAF as a transcriptional repressor, preventing expression of BEC-specific genes, thereby maintaining the differentiation status of LECs. These findings demonstrate that viral miRNAs could influence the differentiation status of infected cells, and thereby contribute to KSHV-induced oncogenesis. © 2010 by Cold Spring Harbor Laboratory Press.
Citation
Hansen, A., Henderson, S., Lagos, D., Nikitenko, L., Coulter, E., Roberts, S., Gratrix, F., Plaisance, K., Renne, R., Bower, M., Kellam, P., & Boshoff, C. (2010). KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Genes & development, 24(2), 195-205. https://doi.org/10.1101/gad.553410
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 23, 2009 |
Publication Date | Jan 15, 2010 |
Deposit Date | May 2, 2022 |
Journal | Genes and Development |
Print ISSN | 0890-9369 |
Publisher | Cold Spring Harbor Laboratory Press |
Peer Reviewed | Peer Reviewed |
Volume | 24 |
Issue | 2 |
Pages | 195-205 |
DOI | https://doi.org/10.1101/gad.553410 |
Public URL | https://hull-repository.worktribe.com/output/3571017 |
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