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Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma
Institution:1. Department of Ophthalmology, Ninth People''s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, PR China;2. Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, PR China;1. Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland;2. Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, University of Dublin, Dublin, Ireland;1. Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53575, USA;2. Duke Eye Center, Duke University, Durham, NC, USA;3. Department of Internal Medicine, Division of Hematology/Oncology, University of Iowa, Iowa City, IA, USA;1. Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China;2. Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
Abstract:Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.
Keywords:Epigenetics  Uveal melanoma  Retinoblastoma  Noncoding RNA  Chromosome conformation  RNA Modifications
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