For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
43
references
 Top references
cited by
33
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      506
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      NAT10‐mediated mRNA N4‐acetylcytidine modification promotes bladder cancer progression

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10‐mediated acetylation modification in bladder cancer remains elusive.

          Methods

          The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10‐deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets.

          Results

          NAT10 was essential for the proliferation, migration, invasion, survival and the stem‐cell‐like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4.

          Conclusions

          In summary, these findings provide new insights into the dynamic characteristics of mRNA's post‐transcriptional modification via NAT10‐dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer.

          Highlights

          1. NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties.

          2. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1.

          3. NAT10 may serve as an effective and novel therapeutic target for BLCA.

          Abstract

          1. NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumorigenic properties.

          2. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1.

          3. NAT10 may serve as an effective and novel therapeutic target for BLCA.

          Related collections

          Most cited references43

          • Record: found
          • Abstract: found
          • Article: not found

          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.
          Article 0 comments Cited 26857 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cancer statistics, 2019

            Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)
            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 cancer incidence, mortality, and survival. Incidence data, available through 2015, 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, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
            Article 0 comments Cited 6542 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.

              Xiao Wang, Boxuan Simen Zhao, Ian A Roundtree … (2015)
              N(6)-methyladenosine (m(6)A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m(6)A-modified mRNA is regulated by an m(6)A reader protein, human YTHDF2, which recognizes m(6)A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that another m(6)A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereas YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m(6)A. Therefore, the m(6)A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.
              Article 0 comments Cited 1071 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Binshen Chen: cbshen@126.com
                Chunxiao Liu: liuchx888@163.com
                Journal
                Journal ID (nlm-ta): Clin Transl Med
                Journal ID (iso-abbrev): Clin Transl Med
                Journal ID (doi): 10.1002/(ISSN)2001-1326
                Journal ID (publisher-id): CTM2
                Title: Clinical and Translational Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2001-1326
                Publication date (Electronic): 06 May 2022
                Publication date Collection: May 2022
                Volume: 12
                Issue: 5 ( doiID: 10.1002/ctm2.v12.5 )
                Electronic Location Identifier: e738
                Affiliations
                [ 1 ] Department of Urology Zhujiang Hospital, Southern Medical University Guangzhou China
                [ 2 ] Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology Sun Yat‐sen University Guangzhou China
                [ 3 ] Department of Urology, The Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China
                Author notes
                [*] [* ] Correspondence

                Chunxiao Liu and Binshen Chen, Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.

                Email: liuchx888@ 123456163.com ; cbshen@ 123456126.com

                Article
                Publisher ID: CTM2738
                DOI: 10.1002/ctm2.738
                PMC ID: 9076013
                PubMed ID: 35522942
                SO-VID: 44778926-11d6-4f1e-92e0-303e3639d862
                Copyright © © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 27 January 2022
                Date received : 19 September 2021
                Date accepted : 29 January 2022
                Page count
                Figures: 9, Tables: 0, Pages: 21, Words: 10024
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81802516
                Categories
                Subject: Research Article
                Subject: Research Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date May 2022
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.5 mode:remove_FC converted:06.05.2022

                ScienceOpen disciplines: Medicine
                Keywords: bladder cancer,mrna,n4‐acetylcytidine,nat10
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: bladder cancer, mrna, n4‐acetylcytidine, nat10

                Comments

                Comment on this article

                scite_

                Similar content506

                See all similar

                Cited by33

                See all cited by

                Most referenced authors950

                See all reference authors