{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:55:01Z","timestamp":1770994501425,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The hypoxia\u2010reoxygenation (H\/R) model helps analyze myocardial infarction triggered by acute myocardial ischemia, which induces cardiomyocyte proliferation and apoptosis. The Gene Expression Omnibus database was used to obtain the GSE74205 and GSE3866 microarray data, including microRNA (miRNA) and messenger RNA profiles, to catalog potential key miRNAs and genes. The role of rno\u2010mir\u2010496 expression in cardiomyocyte proliferation within 10 days of birth was established. The microRNA Target Prediction Database (miRDB) database\u2014via Gene Ontology annotation\u2014predicted hook microtubule tethering protein 3 (Hook3), a key target gene of rno\u2010mir\u2010496, was closely related to cell proliferation. Upregulation of miR\u2010496 related to a significant reduction in apoptosis of H9c2 and human cardiomyocytes treatment with H\/R. Moreover, transfection of H9c2 cells with miR\u2010496 mimics, which were pretreated with H\/R for 12\u2009hours, increased Ki67 levels, proliferating cell nuclear antigen and Bcl\u20102 proteins; and decreased cleaved caspase\u20103 and Bax protein levels, as determined by reverse transcription\u2010polymerase chain reaction and Western blot assays. A dual\u2010luciferase reporter system confirmed that miR\u2010496 targets the Hook3 suppressor. Hook3 overexpression stimulated apoptosis in H\/R\u2010treated cells, thus reducing cell proliferation. Upregulated miR\u2010496 activated phosphatidylinositol\u20103\u2010kinase\/protein kinase B\/mammalian target of rapamycin (PI3K\/Akt\/mTOR) signaling, while Hook3 exhibited the inverse trend in H\/R\u2010treated H9c2 cells. In summary, with Hook3 functionality's aid, miR\u2010496 upregulation defends cells from H\/R\u2010induced apoptosis and stimulates cell proliferation. miR\u2010496 targets Hook3 to trigger the PI3K\/Akt\/mTOR signaling pathway for antiapoptotic and proliferative effects.<\/jats:p>","DOI":"10.1002\/jcb.29316","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T12:26:10Z","timestamp":1566476770000},"page":"698-712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["miR\u2010496 remedies hypoxia reoxygenation\u2013induced H9c2 cardiomyocyte apoptosis via Hook3\u2010targeted PI3k\/Akt\/mTOR signaling pathway activation"],"prefix":"10.1002","volume":"121","author":[{"given":"Yongping","family":"Jin","sequence":"first","affiliation":[{"name":"Department of General Practice The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N1, Shangcheng Road Yiwu City Zhejiang 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