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MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR

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Item Type:Article
Title:MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR
Creators Name:Krause, C.J. and Popp, O. and Thirunarayanan, N. and Dittmar, G. and Lipp, M. and Mueller, G.
Abstract:The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.
Keywords:KSHV, vGPCR, microRNA-34a, Genomic Instability, Genome Maintenance Mechanisms, Animals, Mice
Source:Oncotarget
ISSN:1949-2553
Publisher:Impact Journals
Volume:7
Number:9
Page Range:10414-10432
Date:1 March 2016
Official Publication:https://doi.org/10.18632/oncotarget.7248
PubMed:View item in PubMed

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