title: c-MYC-miRNA circuitry: a central regulator of aggressive B-cell malignancies.
abstract: MYC (c-Myc) deregulation has been frequently associated with aggressive lymphomas and adverse clinical outcome in B-cell malignancies. MYC has been implicated in controlling the expression of miRNAs, and MYC-regulated miRNAs affect virtually all aspects of the hallmarks of MYC-driven lymphomas. Increasing evidence has indicated that there is significant cross-talk between MYC and miRNAs, with MYC regulating expression of a number of miRNAs, resulting in widespread repression of miRNA and, at the same time, MYC being subjected to regulation by miRNAs, leading to sustained MYC activity and the corresponding MYC downstream pathways. Thus, these combined effects of MYC overexpression and downregulation of miRNAs play a central regulatory role in the MYC oncogenic pathways and MYC-driven lymphomagenesis. Here, we provide biological insight on the function of MYC-regulated miRNAs, the mechanisms of MYC-induced miRNA repression, and the complicated feedback circuitry underlying lymphoma progression, as well as potential therapeutic targets in aggressive B-cell lymphomas.
authors.affiliation: Departments of Hematopathology and Laboratory Medicine; H Lee Moffitt Cancer Center and Research Institute at the University of South Florida; Tampa, FL USA.
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Tao
authors.affiliation: Departments of Hematopathology and Laboratory Medicine; H Lee Moffitt Cancer Center and Research Institute at the University of South Florida; Tampa, FL USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Departments of Hematopathology and Laboratory Medicine; H Lee Moffitt Cancer Center and Research Institute at the University of South Florida; Tampa, FL USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc
keywords: aggressive B-cell lymphomas; c-MYC; epigenetic; methylation; miRNA