Gene Set: SAMOLS_TARGETS_OF_KHSV_MIRNAS_UP

Standard name SAMOLS_TARGETS_OF_KHSV_MIRNAS_UP
Systematic name M13045
Brief description Genes up-regulated in 293 cells (embryonic kidney) upon expression of KHSV (Kaposi sarcoma-associated herpesvirus) microRNAs.
Full description or abstract MicroRNAs (miRNAs) are 19 to 23 nucleotide-long RNAs that post-transcriptionally regulate gene expression. Human cells express several hundred miRNAs which regulate important biological pathways such as development, proliferation, and apoptosis. Recently, 12 miRNA genes have been identified within the genome of Kaposi sarcoma-associated herpesvirus; however, their functions are still unknown. To identify host cellular genes that may be targeted by these novel viral regulators, we performed gene expression profiling in cells stably expressing KSHV-encoded miRNAs. Data analysis revealed a set of 81 genes whose expression was significantly changed in the presence of miRNAs. While the majority of changes were below 2-fold, eight genes were down-regulated between 4- and 20-fold. We confirmed miRNA-dependent regulation for three of these genes and found that protein levels of thrombospondin 1 (THBS1) were decreased >10-fold. THBS1 has previously been reported to be down-regulated in Kaposi sarcoma lesions and has known activity as a strong tumor suppressor and anti-angiogenic factor, exerting its anti-angiogenic effect in part by activating the latent form of TGF-beta. We show that reduced THBS1 expression in the presence of viral miRNAs translates into decreased TGF-beta activity. These data suggest that KSHV-encoded miRNAs may contribute directly to pathogenesis by down-regulation of THBS1, a major regulator of cell adhesion, migration, and angiogenesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17500590   Authors: Samols MA,Skalsky RL,Maldonado AM,Riva A,Lopez MC,Baker HV,Renne R
Exact source Table 1S
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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