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Bioinformatics analysis was performed on 85 SVT samples and 15 healthy controls to screen overlapping genes from the key module and differentially expressed genes (DEGs). Expression profiling of overlapping genes, coupled with Receiver Operating Characteristic (ROC) curve analyses, identified FLRT3 as a hub gene. In\u00a0vitro studies utilizing Ang II\u2010stimulated H9C2 cardiomyocytes were undertaken to elucidate the consequences of FLRT3 silencing on cardiomyocyte apoptosis and autophagic processes. Utilizing a combination of techniques such as quantitative reverse\u2010transcription polymerase chain reaction (qRT\u2010PCR), western blotting (WB), flow cytometry, dual\u2010luciferase reporter assays and chromatin immunoprecipitation polymerase chain reaction (ChIP\u2010PCR) assays were conducted to decipher the intricate interactions between FLRT3, the TGF\u2010\u03b2\/SMAD4 signalling cascade and ion channel gene expression. Six genes (AADAC, DSC3, FLRT3, SYT4, PRR9 and SERTM1) demonstrated reduced expression in SVT samples, each possessing significant clinical diagnostic potential. In H9C2 cardiomyocytes, FLRT3 silencing mitigated Ang II\u2010induced apoptosis and modulated autophagy. With increasing TGF\u2010\u03b2 concentration, there was a dose\u2010responsive decline in FLRT3 and SCN5A expression, while both KCNIP2 and KCND2 expressions were augmented. Moreover, a direct interaction between FLRT3 and SMAD4 was observed, and inhibition of SMAD4 expression resulted in increased FLRT3 expression. Our results demonstrated that the TGF\u2010\u03b2\/SMAD4 signalling pathway plays a critical role by regulating FLRT3 expression, with potential implications for ion channel function in SVT.<\/jats:p>","DOI":"10.1111\/jcmm.18237","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T02:45:17Z","timestamp":1710989117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>FLRT3<\/scp> and <scp>TGF<\/scp>\u2010\u03b2\/<scp>SMAD4<\/scp> signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia"],"prefix":"10.1111","volume":"28","author":[{"given":"Yang","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-0934","authenticated-orcid":false,"given":"Wenqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"issue":"9","key":"e_1_2_12_2_1","first-page":"793","article-title":"Diagnosis and management of common types of supraventricular tachycardia","volume":"92","author":"Helton MR","year":"2015","journal-title":"Am Fam Physician"},{"key":"e_1_2_12_3_1","first-page":"307","article-title":"Supraventricular arrhythmias. 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