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      Circular RNA circ‐TNRC6B inhibits the proliferation and invasion of esophageal squamous cell carcinoma cells by regulating the miR‐452‐5p/DAG1 axis

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          Abstract

          Previous studies have uncovered the key role of circular RNAs (circRNAs) in various diseases, including cancer. However, the growth‐inhibitory effects of circRNAs on esophageal squamous cell carcinoma (ESCC) have not been completely elucidated. This study characterized a newly identified circRNA derived from exons 9–13 of TNRC6B (named circ‐TNRC6B). The expression of circ‐TNRC6B in ESCC tissues was markedly downregulated when compared to that in non‐tumor tissues. In 53 ESCC cases, circ‐TNRC6B expression was negatively correlated with the T stage. Multivariate Cox regression analysis showed that circ‐TNRC6B upregulation was an independent protective factor for ESCC patients' prognosis. Overexpression and knockdown functional experiments demonstrated that circ‐TNRC6B inhibited ESCC cell proliferation, migration, and invasion. RNA immunoprecipitation and dual‐luciferase reporter assays demonstrated that circ‐TNRC6B sponges oncogenic miR‐452‐5p to upregulate the expression and activity of DAG1. Treatment with miR‐452‐5p inhibitor partially reversed the circ‐TNRC6B‐induced changes in the biological behavior of ESCC cells. These findings demonstrated that circ‐TNRC6B exerts a tumor‐suppressing effect in ESCC through the miR‐452‐5p/DAG1 axis. Thus, circ‐TNRC6B is a potential prognostic biomarker for the clinical management of ESCC.

          Abstract

          This study identified a previously unknown tumor suppressor circular RNA called circ‐TNRC6B, which was significantly downregulated in esophageal squamous cell carcinoma (ESCC) tissues. circ‐TNRC6B downregulation predicted poor prognosis of patients with ESCC. Functionally, circ‐TNRC6B inhibited the proliferation, migration and invasion of ESCC cells. Mechanistically, circ‐TNRC6B sponged miR‐452‐5p to upregulate the downstream target gene DAG1 in ESCC cells. The findings of this study suggest that circ‐TNRC6B may serve as a novel prognostic biomarker for ESCC.

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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, 2022

            Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (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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              Natural RNA circles function as efficient microRNA sponges.

              Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)
              MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
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                Author and article information

                Contributors
                Meixiang Sang:
                ORCID: https://orcid.org/0000-0001-8295-8463
                meixiangsang@hbydsy.com
                Lingjiao Meng:
                ORCID: https://orcid.org/0000-0001-9316-8774
                ljmeng@hebmu.edu.cn
                Journal
                Journal ID (nlm-ta): Mol Oncol
                Journal ID (iso-abbrev): Mol Oncol
                Journal ID (doi): 10.1002/(ISSN)1878-0261
                Journal ID (publisher-id): MOL2
                Title: Molecular Oncology
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1574-7891
                ISSN (Electronic): 1878-0261
                Publication date (Electronic): 16 April 2023
                Publication date Collection: July 2023
                Volume: 17
                Issue: 7 ( doiID: 10.1002/mol2.v17.7 )
                Pages: 1437-1452
                Affiliations
                [ 1 ] Research Center the Fourth Hospital of Hebei Medical University Shijiazhuang China
                [ 2 ] The Third Department of Surgery the Fourth Hospital of Hebei Medical University Shijiazhuang China
                [ 3 ] Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer the Fourth Hospital of Hebei Medical University Shijiazhuang China
                [ 4 ] Tumor Research Institute the Fourth Hospital of Hebei Medical University Shijiazhuang China
                Author notes
                [*] [* ] Correspondence

                L. Meng and M. Sang, Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China

                Fax: +86 311 86992004

                Tel: +86 311 66696220

                E‐mails: ljmeng@ 123456hebmu.edu.cn ; meixiangsang@ 123456hbydsy.com

                Author information
                https://orcid.org/0000-0001-8295-8463
                https://orcid.org/0000-0001-9316-8774
                Article
                Publisher ID: MOL213432 Other ID: MOLONC-22-0730.R2
                DOI: 10.1002/1878-0261.13432
                PMC ID: 10323880
                PubMed ID: 37014625
                SO-VID: e33ff023-2cbc-461e-a486-c58da8cd1832
                Copyright © © 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
                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 : 07 March 2023
                Date received : 11 September 2022
                Date accepted : 03 April 2023
                Page count
                Figures: 8, Tables: 0, Pages: 1452, Words: 10927
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 82002577
                Categories
                Subject: Non-Coding RNA
                Subject: Esophageal Cancer
                Subject: Biomarkers
                Subject: Research Article
                Subject: Research Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date July 2023
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.1 mode:remove_FC converted:06.07.2023

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circ‐tnrc6b,circular rna,dag1,esophageal squamous cell carcinoma,mir‐452‐5p
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circ‐tnrc6b, circular rna, dag1, esophageal squamous cell carcinoma, mir‐452‐5p

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