{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:52:54Z","timestamp":1791204774401,"version":"4.1.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130010"],"award-info":[{"award-number":["82130010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91949107"],"award-info":[{"award-number":["91949107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014219","name":"MOST | NSFC | National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["81725002"],"award-info":[{"award-number":["81725002"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:p>\n                    Myocardial infarction (MI) is a leading cause of heart failure (HF), associated with morbidity and mortality worldwide. As an essential part of gene expression regulation, the role of alternative polyadenylation (APA) in post-MI HF remains elusive. Here, we revealed a global, APA-mediated, 3\u2032 untranslated region (3\u2032 UTR)-lengthening pattern in both human and murine post-MI HF samples. Furthermore, the 3\u2032 UTR of apoptotic repressor gene,\n                    <jats:italic>AVEN<\/jats:italic>\n                    , is lengthened after MI, contributing to its downregulation.\n                    <jats:italic>AVEN<\/jats:italic>\n                    knockdown increased cardiomyocyte apoptosis, whereas restoration of\n                    <jats:italic>AVEN<\/jats:italic>\n                    expression substantially improved cardiac function. Mechanistically,\n                    <jats:italic>AVEN<\/jats:italic>\n                    3\u2032 UTR lengthening provides additional binding sites for miR-30b-5p and miR-30c-5p, thus reducing AVEN expression. Additionally,\n                    <jats:italic>PABPN1<\/jats:italic>\n                    (poly(A)-binding protein 1) was identified as a potential regulator of\n                    <jats:italic>AVEN<\/jats:italic>\n                    3\u2032 UTR lengthening after MI. Altogether, our findings revealed APA as a unique mechanism regulating cardiac injury in response to MI and also indicated that the APA-regulated gene,\n                    <jats:italic>AVEN<\/jats:italic>\n                    , holds great potential as a critical therapeutic target for treating post-MI HF.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2302482120","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T13:42:03Z","timestamp":1696945323000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["Downregulation of apoptotic repressor\n                    <i>AVEN<\/i>\n                    exacerbates cardiac injury after myocardial infarction"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-9761","authenticated-orcid":false,"given":"Peng","family":"Yu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute, Department of Anthropology and Human Genetics, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-2385","authenticated-orcid":false,"given":"Xiaokai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute, Department of Anthropology and Human Genetics, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute, Department of Anthropology and Human Genetics, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linqi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7007-1072","authenticated-orcid":false,"given":"Ting","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute, Department of Anthropology and Human Genetics, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"},{"name":"State key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010021, China"},{"name":"Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-0937","authenticated-orcid":false,"given":"Aijun","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute, Department of Anthropology and Human Genetics, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai 200438, China"},{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China"},{"name":"Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai 201203, 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Song P. Yu X. Zhang A. Sun Bulk RNA-seq of mouse heart tissue for analyzing gene expression of myocardial infarction progression. NCBI Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE236374. 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