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Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway

AuthorsBueno, María J.; Gómez de Cedrón, Marta; Gómez-López, Gonzalo; Pérez de Castro, Ignacio; Lisio, Lorena di; Montes, Santiago; Martínez, Nerea; Guerrero, Manuel; Sánchez-Martínez, Ruth; Santos, Javier ; Pisano, David G.; Piris, Miguel Ángel; Fernández-Piqueras, José ; Malumbres, Marcos
Issue Date2011
PublisherAmerican Society of Hematology
CitationBlood 117(23): 6255-6266 (2011)
AbstractMany mammalian transcripts contain target sites for multiple miRNAs although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between downregulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the upregulated gene with the highest number of genetic interactions with downregulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach indentifies MYC and multiple Myc targets as a preferential target of downregulated miRNAs in human Burkitt's lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately downregulated in order to enhance critical oncogenes such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs.
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