Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling

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MiRNAs are small non-coding RNAs which decrease gene expression and function as oncogenes or tumor suppressors. Dysregulation of miRNAs is a hallmark of many human cancers. Recently, it was revealed that the miR-17-92 cluster, up-regulated in many cancers, plays a central role in down-regulation of the TGF-β signaling pathway. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gamma-herpesvirus associated with Kaposi’s sarcoma and two lymphoproliferative diseases. KSHV is known to target the TGF-β pathway. Here, we found that two viral latent genes, vFLIP and vCyclin, blunt TGF-β signaling by inducing the host miR-17-92 cluster. Moreover, we confirmed that endothelial cells infected with wt KSHV gave no expression of SMAD2, a key component in the TGF-β pathway. Using a vFLIP vCyclin double knock-out mutant virus gave complete restoration of SMAD2 expression in endothelial cells. This finding reveals a new pathway that KSHV utilizes to promote tumorigenesis and angiogenesis in Kaposi’s sarcoma.

Vyšlo v časopise: Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005255
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005255

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