{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:54:30Z","timestamp":1787003670297,"version":"build-2736575974"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100009664","name":"Sociedad Espa\u00f1ola de Cardiolog\u00eda","doi-asserted-by":"publisher","award":["SEC\/FEC-INV-BAS 22\/034"],"award-info":[{"award-number":["SEC\/FEC-INV-BAS 22\/034"]}],"id":[{"id":"10.13039\/100009664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431G\/2019\/02"],"award-info":[{"award-number":["ED431G\/2019\/02"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["GPC 2016\/022"],"award-info":[{"award-number":["GPC 2016\/022"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","award":["XIV Convocatoria de Ayudas a la Investigaci\u00f3n en Salud"],"award-info":[{"award-number":["XIV Convocatoria de Ayudas a la Investigaci\u00f3n en Salud"]}],"id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-20972-0","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:06:45Z","timestamp":1761127605000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epigenetic regulation of electromechanical continuity might determine phenotypic heterogeneity in SCN5A mutation carriers in Brugada syndrome"],"prefix":"10.1038","volume":"15","author":[{"given":"Isabel","family":"Moscoso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Serrano-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Cebro-M\u00e1rquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta E.","family":"Vilar-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Vidal-Abeij\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Brion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Blanco-Verea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mart\u00ednez-Campelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Feijoo-Band\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Jim\u00e9nez-Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Ram\u00f3n","family":"Gimeno-Blanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Sabater-Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jim\u00e9nez-J\u00e1imez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Gonz\u00e1lez-Juanatey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mois\u00e9s","family":"Rodr\u00edguez-Ma\u00f1ero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Lage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"20972_CR1","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","volume":"20","author":"P Brugada","year":"1992","unstructured":"Brugada, P. & Brugada, J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report. J. Am. Coll. Cardiol. 20, 1391\u20131396 (1992).","journal-title":"J. Am. Coll. Cardiol."},{"key":"20972_CR2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/32675","volume":"392","author":"Q Chen","year":"1998","unstructured":"Chen, Q. et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392, 293\u2013296 (1998).","journal-title":"Nature"},{"key":"20972_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000528375","volume":"32","author":"AV Deica","year":"2023","unstructured":"Deica, A. V., Paduraru, L. F., Paduraru, D. N. & Andronic, O. The SCN5A gene is a predictor of phenotype severity in Brugada syndrome: A comprehensive literature review. Med. Princ. Pract. 32, 1\u20138 (2023).","journal-title":"Med. Princ. Pract."},{"key":"20972_CR4","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.jacc.2018.06.037","volume":"72","author":"J Brugada","year":"2018","unstructured":"Brugada, J., Campuzano, O., Arbelo, E., Sarquella-Brugada, G. & Brugada, R. Present status of Brugada syndrome: JACC state-of-the-art review. J. Am. College Cardiol. 72, 1046\u20131059. https:\/\/doi.org\/10.1016\/j.jacc.2018.06.037 (2018).","journal-title":"J. Am. College Cardiol."},{"key":"20972_CR5","doi-asserted-by":"publisher","first-page":"7155","DOI":"10.3390\/ijms21197155","volume":"21","author":"O Campuzano","year":"2020","unstructured":"Campuzano, O. et al. Update on genetic basis of Brugada syndrome: Monogenic, polygenic or oligogenic?. Int. J. Mol. Sci. 21, 7155. https:\/\/doi.org\/10.3390\/ijms21197155 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.hrthm.2009.09.069","volume":"7","author":"JD Kapplinger","year":"2010","unstructured":"Kapplinger, J. D. et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm 7, 33\u201346 (2010).","journal-title":"Heart Rhythm"},{"key":"20972_CR7","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/CIRCGENETICS.109.853374","volume":"2","author":"V Probst","year":"2009","unstructured":"Probst, V. et al. SCN5A mutations and the role of genetic background in the pathophysiology of brugada syndrome. Circ. Cardiovasc. Genet. 2, 552\u2013557 (2009).","journal-title":"Circ. Cardiovasc. Genet."},{"key":"20972_CR8","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/cge.13552","volume":"97","author":"C Chen","year":"2020","unstructured":"Chen, C. et al. Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta-analysis. Clin. Genet. 97, 198\u2013208. https:\/\/doi.org\/10.1111\/cge.13552 (2020).","journal-title":"Clin. Genet."},{"key":"20972_CR9","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1016\/j.jacc.2016.09.945","volume":"68","author":"T Barwari","year":"2016","unstructured":"Barwari, T., Joshi, A. & Mayr, M. MicroRNAs in cardiovascular disease. J. Am. Coll. Cardiol. 68, 2577\u20132584 (2016).","journal-title":"J. Am. Coll. Cardiol."},{"key":"20972_CR10","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1161\/CIRCRESAHA.116.308434","volume":"120","author":"J Viereck","year":"2017","unstructured":"Viereck, J. & Thum, T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ. Res. 120, 381\u2013399 (2017).","journal-title":"Circ. Res."},{"key":"20972_CR11","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1007\/s00246-019-02160-w","volume":"40","author":"J Jimenez","year":"2019","unstructured":"Jimenez, J. & Rentschler, S. L. Transcriptional and epigenetic regulation of cardiac electrophysiology. Pediatr. Cardiol. 40, 1325\u20131330 (2019).","journal-title":"Pediatr. Cardiol."},{"key":"20972_CR12","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.3390\/ijms22052755","volume":"22","author":"D Carreras","year":"2021","unstructured":"Carreras, D. et al. Epigenetic changes governing scn5a expression in denervated skeletal muscle. Int. J. Mol. Sci. 22, 2755 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR13","doi-asserted-by":"publisher","first-page":"3712","DOI":"10.1021\/pr200339n","volume":"10","author":"P Beltran-Alvarez","year":"2011","unstructured":"Beltran-Alvarez, P., Pagans, S. & Brugada, R. The cardiac sodium channel is post-translationally modified by arginine methylation. J. Proteome. Res. 10, 3712\u20133719 (2011).","journal-title":"J. Proteome. Res."},{"key":"20972_CR14","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"20972_CR15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"20972_CR16","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","volume":"53","author":"M Kanehisa","year":"2025","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. 53, D672\u2013D677 (2025).","journal-title":"Nucleic Acids Res."},{"key":"20972_CR17","doi-asserted-by":"publisher","first-page":"1800065","DOI":"10.1002\/prca.201800065","volume":"12","author":"D Scumaci","year":"2018","unstructured":"Scumaci, D. et al. Integration of \u201cOmics\u201d strategies for biomarkers discovery and for the elucidation of molecular mechanisms underlying Brugada syndrome. Proteomics Clin. Appl. 12, 1800065 (2018).","journal-title":"Proteomics Clin. Appl."},{"key":"20972_CR18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/europace\/euad145","volume":"25","author":"C Steinberg","year":"2023","unstructured":"Steinberg, C. et al. Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome. Europace 25, 145 (2023).","journal-title":"Europace"},{"key":"20972_CR19","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.3390\/ijms21041536","volume":"21","author":"MB Marinas","year":"2020","unstructured":"Marinas, M. B. et al. A microRNA expression profile as non-invasive biomarker in a large arrhythmogenic cardiomyopathy cohort. Int J. Mol. Sci. 21, 1536 (2020).","journal-title":"Int J. Mol. Sci."},{"key":"20972_CR20","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1093\/hmg\/ddv036","volume":"24","author":"S Le Scouarnec","year":"2015","unstructured":"Le Scouarnec, S. et al. Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for brugada syndrome. Hum. Mol. Genet. 24, 2757\u20132763 (2015).","journal-title":"Hum. Mol. Genet."},{"key":"20972_CR21","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1161\/CIRCULATIONAHA.118.035070","volume":"138","author":"SM Hosseini","year":"2018","unstructured":"Hosseini, S. M. et al. Reappraisal of reported genes for sudden arrhythmic death. Circulation 138, 1195\u20131205 (2018).","journal-title":"Circulation"},{"key":"20972_CR22","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.120.002911","author":"YD Wijeyeratne","year":"2020","unstructured":"Wijeyeratne, Y. D. et al. Scn5a mutation type and a genetic risk score associate variably with brugada syndrome phenotype in scn5a families. Circ. Genom. Precis. Med. https:\/\/doi.org\/10.1161\/CIRCGEN.120.002911 (2020).","journal-title":"Circ. Genom. Precis. Med."},{"key":"20972_CR23","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.3390\/cells12192398","volume":"12","author":"B Theisen","year":"2023","unstructured":"Theisen, B., Holtz, A. & Rajagopalan, V. Noncoding RNAs and human induced pluripotent stem cell-derived cardiomyocytes in cardiac arrhythmic Brugada syndrome. Cells 12, 2398 (2023).","journal-title":"Cells"},{"key":"20972_CR24","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.hrthm.2015.02.018","volume":"12","author":"H Daimi","year":"2015","unstructured":"Daimi, H. et al. Regulation of SCN5A by microRNAs: MiR-219 modulates SCN5A transcript expression and the effects of flecainide intoxication in mice. Heart Rhythm 12, 1333\u20131342 (2015).","journal-title":"Heart Rhythm"},{"key":"20972_CR25","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.bj.2019.03.003","volume":"42","author":"H Daimi","year":"2019","unstructured":"Daimi, H. et al. Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What\u2019s behind the scenes?. Biomed. J. 42, 252\u2013260 (2019).","journal-title":"Biomed. J."},{"key":"20972_CR26","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.3390\/ijms23031381","volume":"23","author":"H Daimi","year":"2022","unstructured":"Daimi, H., Lozano-Velasco, E., Aranega, A. & Franco, D. Genomic and non-genomic regulatory mechanisms of the cardiac sodium channel in cardiac arrhythmias. Int. J. Mol. Sci. 23, 1381. https:\/\/doi.org\/10.3390\/ijms23031381 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR27","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.trsl.2012.12.004","volume":"161","author":"GH Kim","year":"2013","unstructured":"Kim, G. H. MicroRNA regulation of cardiac conduction and arrhythmias. Transl Res 161, 381\u2013392 (2013).","journal-title":"Transl Res"},{"key":"20972_CR28","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1093\/europace\/euu366","volume":"18","author":"T Liu","year":"2016","unstructured":"Liu, T. et al. Catheter ablation restores decreased plasma miR-409-3p and miR-432 in atrial fibrillation patients. Europace 18, 92\u201399 (2016).","journal-title":"Europace"},{"key":"20972_CR29","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1016\/j.bbadis.2015.07.016","volume":"1852","author":"Y Zhao","year":"2015","unstructured":"Zhao, Y. et al. Post-transcriptional regulation of cardiac sodium channel gene SCN5A expression and function by miR-192\u20135p. Biochim. Biophys Acta. Mol. Basis Dis. 1852, 2024\u20132034 (2015).","journal-title":"Biochim. Biophys Acta. Mol. Basis Dis."},{"key":"20972_CR30","doi-asserted-by":"publisher","first-page":"4802","DOI":"10.1038\/s41598-017-05001-z","volume":"7","author":"E Sommariva","year":"2017","unstructured":"Sommariva, E. et al. MiR-320a as a potential novel circulating biomarker of Arrhythmogenic CardioMyopathy. Sci. Rep. 7, 4802 (2017).","journal-title":"Sci. Rep."},{"key":"20972_CR31","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.3390\/ijms21041536","volume":"21","author":"MB Marinas","year":"2020","unstructured":"Marinas, M. B. et al. A microRNA expression profile as non-invasive biomarker in a large arrhythmogenic cardiomyopathy cohort. Int. J. Mol. Sci. 21, 1536 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR32","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1093\/europace\/euaa277","volume":"23","author":"Y Ben-Haim","year":"2021","unstructured":"Ben-Haim, Y., Asimaki, A. & Behr, E. R. Brugada syndrome and arrhythmogenic cardiomyopathy: Overlapping disorders of the connexome?. Europace 23, 653\u2013664. https:\/\/doi.org\/10.1093\/europace\/euaa277 (2021).","journal-title":"Europace"},{"key":"20972_CR33","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1016\/j.bbamcr.2016.02.014","volume":"1863","author":"E Zaklyazminskaya","year":"2016","unstructured":"Zaklyazminskaya, E. & Dzemeshkevich, S. The role of mutations in the SCN5A gene in cardiomyopathies. Biochimica et Biophysica Acta Mol. Cell Res. 1863, 1799\u20131805. https:\/\/doi.org\/10.1016\/j.bbamcr.2016.02.014 (2016).","journal-title":"Biochimica et Biophysica Acta Mol. Cell Res."},{"key":"20972_CR34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ppedcard.2014.10.001","volume":"37","author":"A Asimaki","year":"2014","unstructured":"Asimaki, A., Kl\u00e9ber, A. G., MacRae, C. A. & Saffitz, J. E. Arrhythmogenic cardiomyopathy\u2014New insights into disease mechanisms and drug discovery. Progr. Pediatr. Cardiol. 37, 3\u20137. https:\/\/doi.org\/10.1016\/j.ppedcard.2014.10.001 (2014).","journal-title":"Progr. Pediatr. Cardiol."},{"key":"20972_CR35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.forsciint.2017.02.020","volume":"275","author":"X Chen","year":"2017","unstructured":"Chen, X., Chen, L., Chen, Z., Chen, X. & Song, J. Remodelling of myocardial intercalated disc protein connexin 43 causes increased susceptibility to malignant arrhythmias in ARVC\/D patients. Forensic Sci. Int. 275, 14\u201322 (2017).","journal-title":"Forensic Sci. Int."},{"key":"20972_CR36","doi-asserted-by":"publisher","first-page":"4219","DOI":"10.1111\/j.1582-4934.2008.00438.x","volume":"13","author":"LM Fidler","year":"2009","unstructured":"Fidler, L. M. et al. Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations. J. Cell. Mol. Med. 13, 4219\u20134228 (2009).","journal-title":"J. Cell. Mol. Med."},{"key":"20972_CR37","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1016\/j.jacc.2015.08.862","volume":"66","author":"K Nademanee","year":"2015","unstructured":"Nademanee, K. et al. Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome. J. Am. Coll. Cardiol. 66, 1976\u20131986 (2015).","journal-title":"J. Am. Coll. Cardiol."},{"key":"20972_CR38","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.1161\/CIRCULATIONAHA.105.520999","volume":"112","author":"A Frustaci","year":"2005","unstructured":"Frustaci, A. et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 112, 3680\u20133687 (2005).","journal-title":"Circulation"},{"key":"20972_CR39","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1016\/j.jacc.2021.08.010","volume":"78","author":"C Miles","year":"2021","unstructured":"Miles, C. et al. Biventricular myocardial fibrosis and sudden death in patients with Brugada syndrome. J. Am. Coll. Cardiol. 78, 1511\u20131521 (2021).","journal-title":"J. Am. Coll. Cardiol."},{"key":"20972_CR40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1536\/ihj.51.17","volume":"51","author":"K Ohkubo","year":"2010","unstructured":"Ohkubo, K. et al. Right ventricular histological substrate and conduction delay in patients with Brugada syndrome. Int. Heart J. 51, 17\u201323 (2010).","journal-title":"Int. Heart J."},{"key":"20972_CR41","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3390\/jcm9041051","volume":"9","author":"I Galeano-Otero","year":"2020","unstructured":"Galeano-Otero, I. et al. Circulating miR-320a as a predictive biomarker for left ventricular Remodelling in STEMI patients undergoing primary percutaneous coronary intervention. J. Clin. Med. 9, 1051 (2020).","journal-title":"J. Clin. Med."},{"key":"20972_CR42","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1161\/CIRCULATIONAHA.108.814145","volume":"119","author":"X-P Ren","year":"2009","unstructured":"Ren, X.-P. et al. MicroRNA-320 is involved in the regulation of cardiac ischemia\/reperfusion injury by targeting heat-shock protein 20. Circulation 119, 2357\u20132366 (2009).","journal-title":"Circulation"},{"key":"20972_CR43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s11658-018-0105-1","volume":"23","author":"Z-Q Tian","year":"2018","unstructured":"Tian, Z.-Q., Jiang, H. & Lu, Z.-B. MiR-320 regulates cardiomyocyte apoptosis induced by ischemia-reperfusion injury by targeting AKIP1. Cell Mol Biol Lett 23, 41 (2018).","journal-title":"Cell Mol Biol Lett"},{"key":"20972_CR44","doi-asserted-by":"publisher","first-page":"22516","DOI":"10.18632\/aging.203562","volume":"13","author":"F Li","year":"2021","unstructured":"Li, F. et al. miR-320 accelerates chronic heart failure with cardiac fibrosis through activation of the IL6\/STAT3 axis. Aging 13, 22516\u201322527 (2021).","journal-title":"Aging"},{"key":"20972_CR45","doi-asserted-by":"publisher","first-page":"7925","DOI":"10.3390\/ijms21217925","volume":"21","author":"M H\u00e4nninen","year":"2020","unstructured":"H\u00e4nninen, M. et al. Association of miR-21\u20135p, miR-122\u20135p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock. Int. J. Mol. Sci. 21, 7925 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR46","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.3390\/ijms21103485","volume":"21","author":"AV Zhelankin","year":"2020","unstructured":"Zhelankin, A. V. et al. Elevated plasma levels of circulating extracellular miR-320a-3p in patients with paroxysmal atrial fibrillation. Int. J. Mol. Sci. 21, 3485 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"20972_CR47","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1093\/eurheartj\/ehp252","volume":"30","author":"O Catalano","year":"2009","unstructured":"Catalano, O. et al. Magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities. Eur Heart J 30, 2241\u20132248 (2009).","journal-title":"Eur Heart J"},{"key":"20972_CR48","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1161\/CIRCULATIONAHA.110.972612","volume":"123","author":"K Nademanee","year":"2011","unstructured":"Nademanee, K. et al. Prevention of ventricular fibrillation episodes in brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation 123, 1270\u20131279 (2011).","journal-title":"Circulation"},{"key":"20972_CR49","doi-asserted-by":"publisher","first-page":"2747","DOI":"10.1016\/j.jacc.2018.09.037","volume":"72","author":"M Pieroni","year":"2018","unstructured":"Pieroni, M. et al. Electroanatomic and pathologic right ventricular outflow tract abnormalities in patients with Brugada syndrome. J. Am. Coll. Cardiol. 72, 2747\u20132757 (2018).","journal-title":"J. Am. Coll. Cardiol."},{"key":"20972_CR50","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1016\/j.jacep.2020.05.026","volume":"6","author":"E Scheirlynck","year":"2020","unstructured":"Scheirlynck, E. et al. Worse prognosis in brugada syndrome patients with Arrhythmogenic cardiomyopathy features. JACC Clin. Electrophysiol. 6, 1353\u20131363 (2020).","journal-title":"JACC Clin. Electrophysiol."},{"key":"20972_CR51","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s11010-011-1136-3","volume":"362","author":"HF Xu","year":"2012","unstructured":"Xu, H. F. et al. MicroRNA-1 represses Cx43 expression in viral myocarditis. Mol. Cell. Biochem. 362, 141\u2013148 (2012).","journal-title":"Mol. Cell. Biochem."},{"key":"20972_CR52","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1159\/000324012","volume":"26","author":"Y Zhang","year":"2010","unstructured":"Zhang, Y. et al. Tanshinone IIA inhibits miR-1 expression through p38 MAPK signal pathway in post-infarction rat cardiomyocytes. Cell. Physiol. Biochem. 26, 991\u2013998 (2010).","journal-title":"Cell. Physiol. Biochem."},{"key":"20972_CR53","doi-asserted-by":"publisher","first-page":"e70158","DOI":"10.1371\/journal.pone.0070158","volume":"8","author":"A Curcio","year":"2013","unstructured":"Curcio, A. et al. MicroRNA-1 downregulation increases Connexin 43 displacement and induces ventricular Tachyarrhythmias in rodent hypertrophic hearts. PLoS ONE 8, e70158 (2013).","journal-title":"PLoS ONE"},{"key":"20972_CR54","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/nature06321","volume":"450","author":"W Roell","year":"2007","unstructured":"Roell, W. et al. Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia. Nature 450, 819\u2013824 (2007).","journal-title":"Nature"},{"key":"20972_CR55","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1126\/science.7892609","volume":"267","author":"AG Reaume","year":"1995","unstructured":"Reaume, A. G. et al. Cardiac malformation in neonatal mice lacking connexin43. Science 267, 1831\u20131834 (1995).","journal-title":"Science"},{"key":"20972_CR56","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0008-6363(01)00341-8","volume":"51","author":"BC Eloff","year":"2001","unstructured":"Eloff, B. C. et al. High resolution optical mapping reveals conduction slowing in connexin43 deficient mice. Cardiovasc. Res. 51, 681\u2013690 (2001).","journal-title":"Cardiovasc. Res."},{"key":"20972_CR57","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.tcm.2006.05.002","volume":"16","author":"MM Kreuzberg","year":"2006","unstructured":"Kreuzberg, M. M., Willecke, K. & Bukauskas, F. F. Connexin-mediated cardiac impulse propagation: connexin 30.2 slows atrioventricular conduction in mouse heart. Trends Cardiovasc. Med. 16, 266\u2013272 (2006).","journal-title":"Trends Cardiovasc. Med."},{"key":"20972_CR58","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s00232-012-9465-z","volume":"245","author":"JM Rhett","year":"2012","unstructured":"Rhett, J. M., Ongstad, E. L., Jourdan, J. & Gourdie, R. G. Cx43 associates with Na(v)1.5 in the cardiomyocyte perinexus. J. Membr. Biol. 245, 411\u2013422 (2012).","journal-title":"J. Membr. Biol."},{"key":"20972_CR59","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.hrthm.2011.11.025","volume":"9","author":"JA Jansen","year":"2012","unstructured":"Jansen, J. A. et al. Reduced heterogeneous expression of Cx43 results in decreased Nav1.5 expression and reduced sodium current that accounts for arrhythmia vulnerability in conditional Cx43 knockout mice. Heart Rhythm 9, 600\u2013607 (2012).","journal-title":"Heart Rhythm"},{"key":"20972_CR60","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1093\/cvr\/cvu195","volume":"104","author":"E Agullo-Pascual","year":"2014","unstructured":"Agullo-Pascual, E. et al. Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc. Cardiovasc. Res. 104, 371\u2013381 (2014).","journal-title":"Cardiovasc. Res."},{"key":"20972_CR61","doi-asserted-by":"publisher","first-page":"592893","DOI":"10.3389\/fcell.2020.592893","volume":"8","author":"W Li","year":"2020","unstructured":"Li, W. et al. Disease phenotypes and mechanisms of iPSC-derived cardiomyocytes from brugada syndrome patients with a loss-of-function SCN5A mutation. Front. Cell. Dev. Biol. 8, 592893 (2020).","journal-title":"Front. Cell. Dev. Biol."},{"key":"20972_CR62","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1016\/j.febslet.2014.02.008","volume":"588","author":"E Agullo-Pascual","year":"2014","unstructured":"Agullo-Pascual, E., Cerrone, M. & Delmar, M. Arrhythmogenic cardiomyopathy and Brugada syndrome: Diseases of the connexome. FEBS Lett. 588, 1322\u20131330 (2014).","journal-title":"FEBS Lett."},{"key":"20972_CR63","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/nrcardio.2017.103","volume":"14","author":"J Moncayo-Arlandi","year":"2017","unstructured":"Moncayo-Arlandi, J. & Brugada, R. Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome. Nat. Rev. Cardiol. 14, 744\u2013756. https:\/\/doi.org\/10.1038\/nrcardio.2017.103 (2017).","journal-title":"Nat. Rev. Cardiol."},{"key":"20972_CR64","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1161\/CIRCEP.114.002342","volume":"8","author":"M Forkmann","year":"2015","unstructured":"Forkmann, M. et al. Epicardial ventricular tachycardia ablation in a patient with brugada ECG pattern and mutation of PKP2 and DSP genes. Circ. Arrhythm. Electrophysiol. 8, 505\u2013507 (2015).","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"20972_CR65","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ijcard.2014.03.071","volume":"173","author":"S Peters","year":"2014","unstructured":"Peters, S. Arrhythmogenic cardiomyopathy and provocable Brugada ECG in a patient caused by missense mutation in plakophilin-2. Int. J. Cardiol. 173, 317\u2013318 (2014).","journal-title":"Int. J. Cardiol."},{"key":"20972_CR66","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/cvr\/cvw259","volume":"113","author":"SH Vermij","year":"2017","unstructured":"Vermij, S. H., Abriel, H. & Van Veen, T. A. B. Refining the molecular organization of the cardiac intercalated disc. Cardiovascular Res. 113, 259\u2013275. https:\/\/doi.org\/10.1093\/cvr\/cvw259 (2017).","journal-title":"Cardiovascular Res."},{"key":"20972_CR67","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1161\/CIRCULATIONAHA.113.003077","volume":"129","author":"M Cerrone","year":"2014","unstructured":"Cerrone, M. et al. Missense mutations in plakophilin-2 cause sodium current deficit and associate with a brugada syndrome phenotype. Circulation 129, 1092\u20131103 (2014).","journal-title":"Circulation"},{"key":"20972_CR68","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1161\/CIRCULATIONAHA.119.039710","volume":"140","author":"JC Kim","year":"2019","unstructured":"Kim, J. C. et al. Disruption of Ca2+i homeostasis and Connexin 43 hemichannel function in the right ventricle precedes overt Arrhythmogenic cardiomyopathy in Plakophilin-2-Deficient Mice. Circulation 140, 1015\u20131030 (2019).","journal-title":"Circulation"},{"key":"20972_CR69","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1161\/CIRCRESAHA.107.154252","volume":"101","author":"EM Oxford","year":"2007","unstructured":"Oxford, E. M. et al. Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells. Circ. Res. 101, 703\u2013711 (2007).","journal-title":"Circ. Res."},{"key":"20972_CR70","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.3390\/cells8121639","volume":"8","author":"L Puzzi","year":"2019","unstructured":"Puzzi, L. et al. Knock down of Plakophillin 2 dysregulates adhesion pathway through upregulation of miR200b and alters the mechanical properties in cardiac cells. Cells 8, 1639 (2019).","journal-title":"Cells"},{"key":"20972_CR71","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1093\/eurheartj\/ehz308","volume":"40","author":"N Belbachir","year":"2019","unstructured":"Belbachir, N. et al. RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome. Eur. Heart. J. 40, 3081\u20133094 (2019).","journal-title":"Eur. Heart. J."},{"key":"20972_CR72","doi-asserted-by":"publisher","first-page":"390","DOI":"10.7150\/ijbs.10930","volume":"11","author":"N Wang","year":"2015","unstructured":"Wang, N. et al. MicroRNA-23a participates in Estrogen deficiency induced gap junction remodeling of rats by targeting GJA1. Int. J. Biol. Sci. 11, 390\u2013403 (2015).","journal-title":"Int. J. Biol. Sci."},{"key":"20972_CR73","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1007\/s12265-019-09940-y","volume":"13","author":"Y Jin","year":"2020","unstructured":"Jin, Y. et al. Inhibition of MicroRNA-206 ameliorates ischemia-reperfusion arrhythmia in a mouse model by targeting Connexin43. J Cardiovasc Transl Res 13, 584\u2013592 (2020).","journal-title":"J Cardiovasc Transl Res"},{"key":"20972_CR74","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1159\/000445609","volume":"39","author":"X Liu","year":"2016","unstructured":"Liu, X. et al. MiR-223\u20133p as a novel MicroRNA regulator of expression of voltage-gated K+ Channel Kv4.2 in acute myocardial infarction. Cell. Physiol. Biochem. 39, 102\u2013114 (2016).","journal-title":"Cell. Physiol. Biochem."},{"key":"20972_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070158","volume":"8","author":"A Curcio","year":"2013","unstructured":"Curcio, A. et al. MicroRNA-1 downregulation increases Connexin 43 displacement and induces ventricular Tachyarrhythmias in rodent hypertrophic hearts. PLoS ONE 8, e70158 (2013).","journal-title":"PLoS ONE"},{"key":"20972_CR76","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1096\/fj.12-221994","volume":"27","author":"LS Danielson","year":"2013","unstructured":"Danielson, L. S. et al. Cardiovascular dysregulation of miR-17-92 causes a lethal hypertrophic cardiomyopathy and arrhythmogenesis. FASEB J. 27, 1460\u20131467 (2013).","journal-title":"FASEB J."},{"key":"20972_CR77","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.yjmcc.2014.04.024","volume":"74","author":"A Osbourne","year":"2014","unstructured":"Osbourne, A. et al. Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias. J. Mol. Cell. Cardiol. 74, 53\u201363 (2014).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"20972_CR78","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.hlc.2018.09.008","volume":"28","author":"Y Jin","year":"2019","unstructured":"Jin, Y. et al. MicroRNA-206 downregulates Connexin43 in cardiomyocytes to induce cardiac arrhythmias in a transgenic mouse model. Heart Lung. Circ. 28, 1755\u20131761 (2019).","journal-title":"Heart Lung. Circ."},{"key":"20972_CR79","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1242\/jcs.081513","volume":"124","author":"S Valastyan","year":"2011","unstructured":"Valastyan, S. & Weinberg, R. A. Roles for microRNAs in the regulation of cell adhesion molecules. J. Cell. Sci. 124, 999\u20131006 (2011).","journal-title":"J. Cell. Sci."},{"key":"20972_CR80","first-page":"367","volume":"10","author":"H Shi","year":"2022","unstructured":"Shi, H. et al. Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography. Bioact. Mater. 10, 367\u2013377 (2022).","journal-title":"Bioact. Mater."},{"key":"20972_CR81","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.3390\/cells9071649","volume":"9","author":"K Uray","year":"2020","unstructured":"Uray, K., Major, E. & Lontay, B. MicroRNA regulatory pathways in the control of the actin-myosin cytoskeleton. Cells 9, 1649. https:\/\/doi.org\/10.3390\/cells9071649 (2020).","journal-title":"Cells"},{"key":"20972_CR82","doi-asserted-by":"publisher","first-page":"21597","DOI":"10.1038\/s41598-021-01143-3","volume":"11","author":"G Obeng","year":"2021","unstructured":"Obeng, G. et al. miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion. Sci. Rep. 11, 21597 (2021).","journal-title":"Sci. Rep."},{"key":"20972_CR83","doi-asserted-by":"publisher","first-page":"4336","DOI":"10.1093\/eurheartj\/ehae480","volume":"45","author":"A Tarantino","year":"2024","unstructured":"Tarantino, A. et al. NaV1.5 autoantibodies in Brugada syndrome: Pathogenetic implications. Eur. Heart. J. 45, 4336\u20134348 (2024).","journal-title":"Eur. Heart. J."},{"key":"20972_CR84","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050098","author":"D Yang","year":"2021","unstructured":"Yang, D. et al. MicroRNA biophysically modulates cardiac action potential by direct binding to ion channel. Circulation https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.120.050098 (2021).","journal-title":"Circulation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20972-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20972-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20972-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:02:39Z","timestamp":1761130959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20972-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["20972"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-20972-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]},"assertion":[{"value":"7 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Galicia (Date 26 June 2017\/No 2017\/197).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"36885"}}