{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:35:46Z","timestamp":1777552546520,"version":"3.51.4"},"reference-count":32,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>\n                    Acute myocardial infarction is the leading cause of death and disability worldwide. Reperfusion is the main treatment method. However, ischemia\u2013reperfusion (I\/R) injury aggravates tissue and cell damage. In this study, we aim to find a strategy to reduce I\/R injury and promote cardiac function recovery. The expression of AK003290 was downregulated in I\/R injury both\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Overexpression of AK003290 reduced infarction area, oxidative stress, cell apoptosis, and promoted cardiac function recovery. AK003290 was observed to sponge miR-539-3p. Moreover, the expression of miR-539-3p was upregulated in I\/R injury. Overexpression of miR-539-3p reversed the beneficial role of AK003290 in I\/R injury. The target gene of miR-539-3p was proved to be\n                    <jats:italic toggle=\"yes\">ErbB4<\/jats:italic>\n                    , as identified by database prediction, dual-luciferase reporter assay, and pull-down assay. The expression of\n                    <jats:italic toggle=\"yes\">ErbB4<\/jats:italic>\n                    was negatively correlated with the expression of miR-539-3p, but positively correlated with the expression of AK003290. Subsequently, the key downstream proteins were determined. AK003290 promoted p-AKT and bcl-2 expression and inhibited p-ERK1\/2, Bax, cytoplasmic cyto-c, and c-caspase-3 expression. The application of\n                    <jats:italic toggle=\"yes\">ErbB4<\/jats:italic>\n                    siRNA significantly reversed the effect of AK003290 on the expression of these proteins. These results suggest that\n                    <jats:italic toggle=\"yes\">ErbB4<\/jats:italic>\n                    is the key downstream gene, which regulates myocardial cell apoptosis by influencing the miR-539-3p expression. To the best of knowledge, this study is the first to demonstrate that the AK003290\/miR-539-3p\/\n                    <jats:italic toggle=\"yes\">ErbB4<\/jats:italic>\n                    axis regulates myocardial cell apoptosis. These findings provide a potential novel target for the treatment of myocardial I\/R injury.\n                  <\/jats:p>","DOI":"10.1089\/dna.2021.0323","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:01:23Z","timestamp":1640077283000},"page":"1528-1538","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["AK003290 Protects Myocardial Cells Against Apoptosis and Promotes Cardiac Function Recovery Via miR-539-3p\/\n                    <i>ErbB4<\/i>\n                    Axis in Ischemic-Reperfusion Injury"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-7667","authenticated-orcid":false,"given":"Yong","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"e_1_3_5_2_1","first-page":"3034","article-title":"Influence of miR-34a on myocardial apoptosis in rats with acute myocardial infarction through the ERK1\/2 pathway","volume":"23","author":"Bian W.S.","year":"2019","unstructured":"Bian W.S., , Tian F.H., , Jiang L.H., , Sun Y.F., , Wu S.X., , Gao B.F., et al. 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