title: Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway.
abstract: Many 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 down-regulated 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 up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated 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.
authors.affiliation: Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Bueno
authors.forename: Marta
authors.initials: M
authors.lastname: Gómez de Cedrón
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez de Castro
authors.forename: Lorena
authors.initials: L
authors.lastname: Di Lisio
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Nerea
authors.initials: N
authors.lastname: Martínez
authors.forename: Manuel
authors.initials: M
authors.lastname: Guerrero
authors.forename: Ruth
authors.initials: R
authors.lastname: Sánchez-Martínez
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Piris
authors.forename: José
authors.initials: J
authors.lastname: Fernández-Piqueras
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D035683:MicroRNAs; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm