Epigenetic modification and a role for the E3 ligase RNF40 in cancer development and metastasis

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Abstract

RNF40 (OMIM: 607700) is a really interesting new gene (RING) finger E3 ubiquitin ligase containing multiple coiled-coil domains and a C-terminal RING finger motif, which engage in protein–DNA and protein–protein interactions. RNF40 encodes a polypeptide of 1001 amino acids with a predicted molecular mass of 113,678 Da. RNF40 and its paralog RNF20 form a stable heterodimer complex that can monoubiquitylate histone H2B at lysine 120 as well as other nonhistone proteins. Cancer is a major public health problem and the second leading cause of death. Through its protein ubiquitylation activity, RNF40 acts as a tumor suppressor or oncogene to play major epigenetic roles in cancer development, progression, and metastasis, highlighting the essential function of RNF40 and the importance of studying it. In this review, we summarize current knowledge about RNF40 gene structure and the role of RNF40 in histone H2B monoubiquitylation, DNA damage repair, apoptosis, cancer development, and metastasis. We also underscore challenges in applying this information to cancer prognosis and prevention and highlight the urgent need for additional investigations of RNF40 as a potential target for cancer therapeutics.

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Regulation of chromatin by histone modifications.

Andrew Bannister, Tony Kouzarides (2011)

Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.

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Author and article information

Contributors

Junjiang Fu:

ORCID: http://orcid.org/0000-0002-0708-2200

fujunjiang@hotmail.com

Jaehoon Kim:

ORCID: http://orcid.org/0000-0003-4035-0438

kimjaehoon@kaist.edu

Jiangzhou Peng:

ORCID: http://orcid.org/0000-0002-8058-8988

jiangzhou83@163.com

Journal

Journal ID (nlm-ta): Oncogene

Journal ID (iso-abbrev): Oncogene

Title: Oncogene

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 0950-9232

ISSN (Electronic): 1476-5594

Publication date (Electronic): 16 November 2020

Publication date PMC-release: 16 November 2020

Publication date (Print): 2021

Volume: 40

Issue: 3

Pages: 465-474

Affiliations

[1 ]GRID grid.410578.f, ISNI 0000 0001 1114 4286, Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, , Southwest Medical University, ; Luzhou, 646000 Sichuan China

[2 ]GRID grid.413039.c, ISNI 0000 0001 0805 7368, Post Graduation Department of Studies and Research in Biotechnology, Teresian Research Center, , Teresian College (Affiliated to University of Mysore), ; Siddhartha Nagara, Mysore, Karnataka 570011 India

[3 ]GRID grid.37172.30, ISNI 0000 0001 2292 0500, Department of Biological Sciences, , Korea Advanced Institute of Science and Technology, ; Daejeon, 34141 South Korea

[4 ]GRID grid.413107.0, Department of Thoracic Surgery, , The Third Affiliated Hospital of Southern Medical University, ; Guangzhou, 510500 Guangdong China

Author information

Junjiang Fu http://orcid.org/0000-0002-0708-2200

Kyathegowdanadoddi Srinivasa Balaji http://orcid.org/0000-0002-7236-8993

Jaehoon Kim http://orcid.org/0000-0003-4035-0438

Jiangzhou Peng http://orcid.org/0000-0002-8058-8988

Article

Publisher ID: 1556

DOI: 10.1038/s41388-020-01556-w

PMC ID: 7819849

PubMed ID: 33199825

SO-VID: aadb331b-cead-47f3-84fa-bea03862dd1b

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 23 March 2020

Date revision received : 15 October 2020

Date accepted : 2 November 2020

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 82073263

Award ID: 81172049

Award Recipient : Junjiang Fu

Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);

Award ID: 2018R1A5A1024261 and 2019R1A2C2090830

Award Recipient : Jaehoon Kim

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer genetics,epigenetics

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer genetics, epigenetics

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Epigenetic modification and a role for the E3 ligase RNF40 in cancer development and metastasis

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Karger: Oncology

Most cited references 91

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Cancer statistics, 2020

Regulation of chromatin by histone modifications.

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