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      Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

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          Abstract

          SET domain-containing 2 (SETD2) is a lysine methyltransferase that catalyzes histone H3 lysine36 trimethylation (H3K36me3) and has been revealed to play important roles in the regulation of transcriptional elongation, RNA splicing, and DNA damage repair. SETD2 mutations have been documented in several cancers, including clear cell renal cell carcinoma (ccRCC). SETD2 deficiency is associated with cancer occurrence and progression by regulating autophagy flux, general metabolic activity, and replication fork speed. Therefore, SETD2 is considered a potential epigenetic therapeutic target and is the subject of ongoing research on cancer-related diagnosis and treatment. This review presents an overview of the molecular functions of SETD2 in H3K36me3 regulation and its relationship with ccRCC, providing a theoretical basis for subsequent antitumor therapy based on SETD2 or H3K36me3 targets.

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          Most cited references117

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          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cancer statistics, 2022

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) 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 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                21 March 2023
                2023
                : 13
                : 1114461
                Affiliations
                [1] 1Department of Biological Repositories, Zhongnan Hospital of Wuhan University , Wuhan, China
                [2] 2Department of Urology, Zhongnan Hospital of Wuhan University , Wuhan, China
                [3] 3Human Genetic Resources Preservation Center of Hubei Province , Wuhan, China
                [4] 4Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences , Wuhan, China
                [5] 5Medical Research Institute, Wuhan University , Wuhan, China
                Author notes

                Edited by: Linhui Wang, Second Military Medical University, China

                Reviewed by: Wei Huang, Capital Medical University, China; Haifeng Yang, Thomas Jefferson University, United States

                This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2023.1114461
                10070805
                37025591
                e6eaaa75-d2b9-41b0-b881-bab121258837
                Copyright © 2023 Yu, Qian, Wang, Xiao, Zhu and Ju

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 December 2022
                : 09 March 2023
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 117, Pages: 13, Words: 5168
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                This study was supported by the National Natural Science Foundation of China (31900902), Hubei Province health and family planning scientific research project (WJ2023M063), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2020-PT320-004).
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                setd2,clear cell renal cell carcinoma (ccrcc),h3k36me3,epigenetic regulation,mutation

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