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      Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression

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          Abstract

          Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          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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            Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer

            Rodrigo Dienstmann, Louis Vermeulen, Justin Guinney … (2017)
            In this Review, Dienstmann et al. analyse the complex nature of colorectal cancer and the different subtypes in which this disease can be classified, advocating for a 'multi-molecular' perspective for the development of therapies to treat it.
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              Breaking the chains: structure and function of the deubiquitinases.

              David Komander, Sylvie Urbé, M Clague (2009)
              Ubiquitylation is a reversible protein modification that is implicated in many cellular functions. Recently, much progress has been made in the characterization of a superfamily of isopeptidases that remove ubiquitin: the deubiquitinases (DUBs; also known as deubiquitylating or deubiquitinating enzymes). Far from being uniform in structure and function, these enzymes display a myriad of distinct mechanistic features. The small number (<100) of DUBs might at first suggest a low degree of selectivity; however, DUBs are subject to multiple layers of regulation that modulate both their activity and their specificity. Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets.
              Article 0 comments Cited 301 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhengyi Liu:
                ORCID: http://orcid.org/0000-0001-9370-1508
                zhengyiliu159@126.com
                Journal
                Journal ID (nlm-ta): Cell Death Dis
                Journal ID (iso-abbrev): Cell Death Dis
                Title: Cell Death & Disease
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2041-4889
                Publication date (Electronic): 13 February 2024
                Publication date PMC-release: 13 February 2024
                Publication date Collection: February 2024
                Volume: 15
                Issue: 2
                Electronic Location Identifier: 137
                Affiliations
                [1 ]Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, ( https://ror.org/04c4dkn09) Heifei, 230001 China
                [2 ]GRID grid.54549.39, ISNI 0000 0004 0369 4060, Department of Gastrointestinal Surgery, Sichuan Provincial People’s Hospital, , University of Electronic Science and Technology of China, ; Chengdu, 610000 Sichuan China
                [3 ]GRID grid.414011.1, ISNI 0000 0004 1808 090X, Department of Breast Surgery, , Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, ; Zhengzhou, 450000 Henan China
                [4 ]Microbiome Laboratory, People’s Hospital of Zhengzhou University, ( https://ror.org/04ypx8c21) Zhengzhou, 450000 China
                [5 ]GRID grid.207374.5, ISNI 0000 0001 2189 3846, Translational Research Institute, Henan Provincial and Zhengzhou City Key Laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Academy of Medical Sciences, , Zhengzhou University, ; Zhengzhou, 450000 Henan China
                [6 ]Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, ( https://ror.org/003xyzq10) Zhengzhou, 450000 China
                Author information
                http://orcid.org/0000-0001-9370-1508
                Article
                Publisher ID: 6526
                DOI: 10.1038/s41419-024-06526-8
                PMC ID: 10864350
                PubMed ID: 38351178
                SO-VID: 5a541f19-13ee-4e86-add3-9c0b1ea40bef
                Copyright © © The Author(s) 2024
                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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 11 July 2023
                Date revision received : 25 January 2024
                Date accepted : 31 January 2024
                Funding
                Funded by: Science and technology project of Henan Province(No. 222102310037)
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Associazione Differenziamento e Morte Cellulare ADMC 2024

                ScienceOpen disciplines: Cell biology
                Keywords: colorectal cancer
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: colorectal cancer

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