Role of novel histone modifications in cancer

// Muthu K. Shanmugam 1 , Frank Arfuso 2 , Surendar Arumugam 10 , Arunachalam Chinnathambi 3 , Bian Jinsong 1 , Sudha Warrier 4 , Ling Zhi Wang 1,5 , Alan Prem Kumar 1,5,6,7,8 , Kwang Seok Ahn 9 , Gautam Sethi 1 and Manikandan Lakshmanan 10,11 1 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 2 Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia 3 Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia 4 Division of Cancer Stem Cells and Cardiovascular Regeneration, School of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore, India 5 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore 6 Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia 7 National University Cancer Institute, National University Health System, Singapore, Singapore 8 Department of Biological Sciences, University of North Texas, Denton, Texas, USA 9 College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Korea 10 Institute of Molecular and Cell Biology, A*STAR, Biopolis Drive, Proteos, Singapore, Singapore 11 Department of Pathology, National University Hospital Singapore, Singapore, Singapore Correspondence to: Manikandan Lakshmanan, email: // Gautam Sethi, email: // Kwang Seok Ahn, email: // Keywords : cancer; histones; oncogenes; tumor suppressor genes; ubiquitination Received : October 11, 2017 Accepted : December 01, 2017 Published : December 17, 2017 Abstract Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation. However, there are several other novel post-translational modifications that have been observed in recent times such as neddylation, sumoylation, glycosylation, phosphorylation, poly-ADP ribosylation, ubiquitination as well as transcriptional regulation and these have been briefly discussed in this article. We have also highlighted the diverse epigenetic changes that occur during the process of tumorigenesis and described the role of histone modifications that can occur on tumor suppressor genes as well as oncogenes, which regulate tumorigenesis and can thus form the basis of novel strategies for cancer therapy.