{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:46:35Z","timestamp":1788630395260,"version":"build-2803163510"},"reference-count":30,"publisher":"Portland Press Ltd.","issue":"9","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Bureau of Hebei Province","award":["No. 19277787D"],"award-info":[{"award-number":["No. 19277787D"]}]},{"name":"Science and Technology Bureau of Hebei Province","award":["No. 199776249D"],"award-info":[{"award-number":["No. 199776249D"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>MicroRNA-21 (miR-21) plays an anti-apoptotic role following ischemia\u2013reperfusion (I\/R) injury (IRI) in vivo; however, its underlying mechanism remains unclear. The present study explored the effects of miR-21 and homeodomain interacting protein kinase 3 (HIPK3) on cardiomyocyte apoptosis induced by hypoxia\/reoxygenation (H\/R) in vitro. To this end, the rat cardiomyocyte H9C2 cell line was exposed to H\/R and the roles of miR-21 and HIPK3 in regulating cell viability and apoptosis were evaluated by cell counting kit-8 assay, terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling, and flow cytometry. Immunofluorescence and Western blotting were performed to detect the expression\/phosphorylation of apoptosis-related proteins. miR-21 expression was measured with quantitative real-time polymerase chain reaction. The putative interaction between miR-21 and HIPK3 was evaluated using the luciferase reporter assay. Our results showed that (i) miR-21 overexpression or HIPK3 down-regulation significantly attenuated H9C2 cells apoptosis after H\/R, (ii) suppression of miR-21 expression promoted apoptosis, (iii) miR-21 overexpression inhibited HIPK3 expression, (iv) HIPK3 was the direct and main target of miR-21, (v) miR-21\/HIPK3 formed part of a reciprocal, negative feedback loop, and (vi) HIPK3 down-regulation decreased FAS-mediated apoptosis by inhibiting the phosphorylation of FADD, which subsequently inhibited the expression of BAX and cleaved caspase-3 and increased the expression of BCL2. Our study indicates that miR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression, which could eventually have important clinical implications for patients with acute myocardial infarction.<\/jats:p>","DOI":"10.1042\/bsr20230014","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:50:49Z","timestamp":1692100249000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MiR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression"],"prefix":"10.1042","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1911-0854","authenticated-orcid":false,"given":"Xinyu","family":"Wang","sequence":"first","affiliation":[{"name":"1College of Postgraduate, Hebei North University, Zhangjiakou, Hebei, China"},{"name":"2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlong","family":"Zhai","sequence":"additional","affiliation":[{"name":"3Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongli","family":"Wang","sequence":"additional","affiliation":[{"name":"4Department of Physical Examination Center, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"He","sequence":"additional","affiliation":[{"name":"2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Ma","sequence":"additional","affiliation":[{"name":"5Department of Internal Medicine, Hebei General Hospital, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanying","family":"Xing","sequence":"additional","affiliation":[{"name":"6Hebei Key Laboratory of Metabolic Disease, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-5940","authenticated-orcid":false,"given":"Yifang","family":"Guo","sequence":"additional","affiliation":[{"name":"1College of Postgraduate, Hebei North University, Zhangjiakou, Hebei, China"},{"name":"2Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"2023090510311190900_B1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: a neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J. 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