title: Repressing the repressor: a new mode of MYC action in lymphomagenesis.
abstract: The MYC oncogene is often mutated or amplified in human tumors resulting in increased activity of the transcription factor. Recent evidence suggested that MYC not only regulates expression of protein-coding genes directly, but also controls expression of miRNAs thereby using a second mode to impact on gene expression programs. The importance of miRNAs in MYC-driven tumorigenesis has been enlightened by studying cell line and murine lymphoma models with conditional expression of MYC. The application of microarray technology revealed both MYC-induced and MYC-repressed miRNAs. A miRNA consistently repressed by MYC in multiple tumors was miR-26a indicating that this miRNA might have strong tumor suppressor function for MYC-induced lymphomas. Indeed, ectopic miR-26a expression in MYC-dependent cells resulted in attenuated proliferation and impaired cell cycle progression. When the effector pathway for miR-26a was elucidated, the Polycomb complex protein EZH2, a global regulator of gene expression, was identified as a direct target. The suppression of miR-26a mediated attenuation of EZH2 expression by MYC was shown to play a critical role in lymphomagenesis. Thus, MYC-induced oncogenesis does not only depend on direct targeting of protein-coding genes, but also on modulating them via deregulation of their targeting miRNAs, thereby significantly impacting lymphomagenesis.
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Sander
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D035683:MicroRNAs; D012097:Repressor Proteins