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      Role of N 6‑methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review)

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          Abstract

          Prostate cancer (PCa) affects males of all racial and ethnic groups, and leads to higher rates of mortality in those belonging to a lower socioeconomic status due to the late detection of the disease. PCa affects middle-aged males between the ages of 45 and 60 years, and is the highest cause of cancer-associated mortality in Western countries. As the most abundant and common mRNA modification in higher eukaryotes, N 6-methyladenosine (m 6A) is widely distributed in mammalian cells and influences various aspects of mRNA metabolism. Recent studies have found that abnormal expression levels of various m 6A regulators significantly affect the development and progression of various types of cancer, including PCa. The present review discusses the influence of m 6A regulatory factors on the pathogenesis and progression of PCa through mRNA modification based on the current state of research on m 6A methylation modification in PCa. It is considered that the treatment of PCa with micro-molecular drugs that target the epigenetics of the m 6A regulator to correct abnormal m 6A modifications is a direction for future research into current diagnostic and therapeutic approaches for PCa.

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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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            Cancer statistics in China and United States, 2022: profiles, trends, and determinants

            Background: The cancer burden in the United States of America (USA) has decreased gradually. However, China is experiencing a transition in its cancer profiles, with greater incidence of cancers that were previously more common in the USA. This study compared the latest cancer profiles, trends, and determinants between China and USA. Methods: This was a comparative study using open-source data. Cancer cases and deaths in 2022 were calculated using cancer estimates from GLOBOCAN 2020 and population estimates from the United Nations. Trends in cancer incidence and mortality rates in the USA used data from the Surveillance, Epidemiology, and End Results program and National Center for Health Statistics. Chinese data were obtained from cancer registry reports. Data from the Global Burden of Disease 2019 and a decomposition method were used to express cancer deaths as the product of four determinant factors. Results: In 2022, there will be approximately 4,820,000 and 2,370,000 new cancer cases, and 3,210,000 and 640,000 cancer deaths in China and the USA, respectively. The most common cancers are lung cancer in China and breast cancer in the USA, and lung cancer is the leading cause of cancer death in both. Age-standardized incidence and mortality rates for lung cancer and colorectal cancer in the USA have decreased significantly recently, but rates of liver cancer have increased slightly. Rates of stomach, liver, and esophageal cancer decreased gradually in China, but rates have increased for colorectal cancer in the whole population, prostate cancer in men, and other seven cancer types in women. Increases in adult population size and population aging were major determinants for incremental cancer deaths, and case-fatality rates contributed to reduced cancer deaths in both countries. Conclusions: The decreasing cancer burden in liver, stomach, and esophagus, and increasing burden in lung, colorectum, breast, and prostate, mean that cancer profiles in China and the USA are converging. Population aging is a growing determinant of incremental cancer burden. Progress in cancer prevention and care in the USA, and measures to actively respond to population aging, may help China to reduce the cancer burden.
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              YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA

              N 6 -methyladenosine (m 6 A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and tissue development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and decay, via the recognition by selective binding proteins. In the cytoplasm, m 6 A binding protein YTHDF1 facilitates translation of m 6 A-modified mRNAs, and YTHDF2 accelerates the decay of m 6 A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m 6 A binder of the YTH (YT521-B homology) domain family, remains unknown. Here, we report that YTHDF3 promotes protein synthesis in synergy with YTHDF1, and affects methylated mRNA decay mediated through YTHDF2. Cells deficient in all three YTHDF proteins experience the most dramatic accumulation of m 6 A-modified transcripts. These results indicate that together with YTHDF1 and YTHDF2, YTHDF3 plays critical roles to accelerate metabolism of m 6 A-modified mRNAs in the cytoplasm. All three YTHDF proteins may act in an integrated and cooperative manner to impact fundamental biological processes related to m 6 A RNA methylation.
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                Author and article information

                Journal
                Oncol Rep
                Oncol Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                June 2024
                13 May 2024
                13 May 2024
                : 51
                : 6
                : 88
                Affiliations
                [1 ]Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Westlake University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
                [2 ]Fourth Clinical Medical College of Zhejiang Chinese Medical University, Affiliated Hangzhou First People's Hospital, Hangzhou, Zhejiang 310051, P.R. China
                [3 ]Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
                [4 ]Department of Urology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310007, P.R. China
                Author notes
                Correspondence to: Ms. Qiaoping Xu, Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Westlake University School of Medicine, 261 Huan Sha Road, Hangzhou, Zhejiang 310006, P.R. China, E-mail: xqp1984@ 123456126.com
                Professor Feng Gao, Department of Urology, Hangzhou Hospital of Traditional Chinese Medicine, 453 Ti Yu Chang Road, Hangzhou, Zhejiang 310007, P.R. China, E-mail: friendgao@ 123456yeah.net
                [*,**]

                Contributed equally

                Article
                OR-51-6-08747
                10.3892/or.2024.8747
                11110010
                38757383
                9a11548b-37a4-4d80-90d5-735241c4f89e
                Copyright: © 2024 Pan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 November 2023
                : 19 April 2024
                Funding
                Funded by: Key Medical Discipline of Hangzhou City
                Award ID: 2021-21
                Funded by: Key Medical Discipline of Zhejiang Province
                Award ID: 2018-2-3
                Funded by: Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province
                Award ID: 2020E10021
                Funded by: Zhejiang Province Medical and Health Science and Technology Program
                Award ID: 2023KY933
                Funded by: Zhejiang Traditional Chinese Medicine Science and Technology Project
                Award ID: 2023ZL565
                The present study was funded by the Key Medical Discipline of Hangzhou City (grant no. 2021-21), the Key Medical Discipline of Zhejiang Province (grant no. 2018-2-3), the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (grant no. 2020E10021), the Zhejiang Province Medical and Health Science and Technology Program (grant no. 2023KY933), and the Zhejiang Traditional Chinese Medicine Science and Technology Project (grant no. 2023ZL565).
                Categories
                Review

                prostate cancer,n6-methyladenosine,regulator,genetics,rna
                prostate cancer, n6-methyladenosine, regulator, genetics, rna

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