KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming.

Genes Dev 2010 Jan;24(2):195-205

Cancer Research UK Viral Oncology Group, University College London Cancer Institute, University College London, London WC1E 6BT, United Kingdom.

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 viral-induced 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.

Download full-text PDF

Source
http://dx.doi.org/10.1101/gad.553410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807354PMC
January 2010
3 Reads

Publication Analysis

Top Keywords

endothelial cells
16
kaposi sarcoma
12
kshv-encoded mirnas
8
differentiation status
8
lecs becs
8
cells
6
endothelial
5
maf musculoaponeurotic
4
contribute viral-induced
4
mirnas contribute
4
demonstrate mirnas
4
lesions demonstrate
4
viral-induced reprogramming
4
reprogramming silencing
4
cellular transcription
4
factor maf
4
sarcoma lesions
4
silencing cellular
4
transcription factor
4
expression kshv-encoded
4

Similar Publications