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This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW\/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW\/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt\/\u03b2-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and \u03b2-catenin protein level, which negated the protective effects of USP2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt\/\u03b2-catenin axis and alleviating cardiac hypertrophy-induced heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-024-03748-8","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T03:03:39Z","timestamp":1706670219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2\/JUP\/Akt\/\u03b2-catenin cascade"],"prefix":"10.1186","volume":"24","author":[{"given":"Weinian","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjiang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongquan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"3748_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","volume":"97","author":"I Shimizu","year":"2016","unstructured":"Shimizu I, Minamino T. 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