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      Epigenetics in ovarian cancer: premise, properties, and perspectives

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          Abstract

          Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemical therapy increase patient mortality. Therefore, it is both urgent and important to identify biomarkers facilitating early identification and novel agents preventing recurrence. Accumulating evidence demonstrates that epigenetic aberrations (particularly histone modifications) are crucial in tumor initiation and development. Histone acetylation and methylation are respectively regulated by acetyltransferases-deacetylases and methyltransferases-demethylases, both of which are implicated in ovarian cancer pathogenesis. In this review, we summarize the most recent discoveries pertaining to ovarian cancer development arising from the imbalance of histone acetylation and methylation, and provide insight into novel therapeutic interventions for the treatment of ovarian carcinoma.

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          Most cited references162

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          Cancer genes and the pathways they control.

          The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized. The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation.
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            The diverse functions of histone lysine methylation.

            Covalent modifications of histone tails have fundamental roles in chromatin structure and function. One such modification, lysine methylation, has important functions in many biological processes that include heterochromatin formation, X-chromosome inactivation and transcriptional regulation. Here, we summarize recent advances in our understanding of how lysine methylation functions in these diverse biological processes, and raise questions that need to be addressed in the future.
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              Histone methyltransferase activity of a Drosophila Polycomb group repressor complex.

              Polycomb group (PcG) proteins maintain transcriptional repression during development, likely by creating repressive chromatin states. The Extra Sex Combs (ESC) and Enhancer of Zeste [E(Z)] proteins are partners in an essential PcG complex, but its full composition and biochemical activities are not known. A SET domain in E(Z) suggests this complex might methylate histones. We purified an ESC-E(Z) complex from Drosophila embryos and found four major subunits: ESC, E(Z), NURF-55, and the PcG repressor, SU(Z)12. A recombinant complex reconstituted from these four subunits methylates lysine-27 of histone H3. Mutations in the E(Z) SET domain disrupt methyltransferase activity in vitro and HOX gene repression in vivo. These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing.
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                Author and article information

                Contributors
                qilian176@163.com
                taotaovip2005@foxmail.com
                rxiangnile@qq.com
                497326318@qq.com
                316353678@qq.com
                263577827@qq.com
                624204837@qq.com
                8085603@qq.com
                718012373@qq.com
                361208603@qq.com
                296324961@qq.com
                44128579@qq.com
                3489719452@qq.com
                573040821@qq.com
                +86-18180609005 , whjscdx@163.com
                +86-18108089011 , ljzhao89@163.com
                +86-13551070137 , taotaovip2005@163.com
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                31 July 2018
                31 July 2018
                2018
                : 17
                : 109
                Affiliations
                [1 ]ISNI 0000 0004 1757 9397, GRID grid.461863.e, Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, , West China Second University Hospital, Sichuan University and Collaborative Innovation Center, ; Chengdu, 610041 People’s Republic of China
                [2 ]ISNI 0000 0001 2182 8825, GRID grid.260463.5, Nanchang University, ; Nanchang, People’s Republic of China
                [3 ]ISNI 0000 0000 9479 9538, GRID grid.412600.1, Sichuan Normal University Affiliated Middle School, ; Chengdu, People’s Republic of China
                [4 ]ISNI 0000 0004 0442 8581, GRID grid.412726.4, Department of Emergency Medicine, , Thomas Jefferson University Hospital, ; Philadelphia, USA
                [5 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Surgery, Emergency Medicine, Kaiser Santa Clara Medical Center, , Affiliate of Stanford University, ; Stanford, USA
                [6 ]Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong China
                [7 ]ISNI 0000 0004 1757 9397, GRID grid.461863.e, Department of Pathology, , West China Second University Hospital, Sichuan University, ; Chengdu, People’s Republic of China
                Article
                855
                10.1186/s12943-018-0855-4
                6069741
                30064416
                9e231807-974f-4d08-b966-effa75ba8c13
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 December 2017
                : 11 July 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81402396
                Award ID: 81773119
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                ovarian cancer,epigenetics,histone methylaiton,histone acetylation
                Oncology & Radiotherapy
                ovarian cancer, epigenetics, histone methylaiton, histone acetylation

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