title: Polycomb genes, miRNA, and their deregulation in B-cell malignancies.
abstract: Posttranslational modifications of histone proteins represent a fundamental means to define distinctive epigenetic states and regulate gene expression during development and differentiation. Aberrations in various chromatin-modulation pathways are commonly used by tumors to initiate and maintain oncogenesis, including lymphomagenesis. Recently, increasing evidence has demonstrated that polycomb group (PcG) proteins, a subset of histone-modifying enzymes known to be crucial for B-cell maturation and differentiation, play a central role in malignant transformation of B cells. PcG hyperactivity in B-cell lymphomas is caused by overexpression or recurrent mutations of PcG genes and deregulation of microRNAs (miRNAs) or transcription factors such as c-MYC, which regulate PcG expression. Interplays of PcG and miRNA deregulations often establish a vicious signal-amplification loop in lymphoma associated with adverse clinical outcomes. Importantly, aberrant enzymatic activities associated with polycomb deregulation, notably those caused by EZH2 gain-of-function mutations, have provided a rationale for developing small-molecule inhibitors as novel therapies. In this review, we summarize our current understanding of PcG-mediated gene silencing, interplays of PcG with other epigenetic regulators such as miRNAs during B-cell differentiation and lymphomagenesis, and recent advancements in targeted strategies against PcG as promising therapeutics for B-cell malignancies.
authors.affiliation: Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, and.
authors.forename: Gang Greg
authors.identifier: http://orcid.org/0000-0002-7210-9940
authors.initials: GG
authors.lastname: Wang
authors.affiliation: Center for Integrative Chemical Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, NC; and.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Konze
authors.affiliation: Departments of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tao
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D063146:Polycomb-Group Proteins