{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:28:07Z","timestamp":1788877687825,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1301402"],"award-info":[{"award-number":["2016YFC1301402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetic cardiomyopathy (DCM) is one of the serious complications of the accumulated cardiovascular system in the long course of diabetes. To date, there is no effective treatment available for DCM. Circular RNA (circRNA) is a novel r2egulatory RNA that participates in a variety of cardiac pathological processes. However, the regulatory role of circular RNA MAP3K5 (circMAP3K5) in DCM is largely unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Microarray analysis of DCM rats' heart circular RNAs was performed and the highly species\u2010conserved circRNA mitogen\u2010activated protein kinase kinase kinase 5 (circMAP3K5) was identified, which participates in DCM processes. High glucose\u2010provoked cardiotoxicity leads to the up\u2010regulation of circMAP3K5, which mechanistically contributes to cardiomyocyte cell death. Also, in high glucose\u2010induced H9c2 cardiomyocytes, the level of apoptosis was significantly increased, as well as the expression of circMAP3K5. In contrast, the depletion of circMAP3K5 could reduce high glucose\u2010induced apoptosis in cardiomyocytes. In terms of mechanism, circMAP3K5 acts as a miR\u201022\u20103p sponge and miR\u201022\u20103p directly target death\u2010associated protein kinase 2 (DAPK2) in H9c2 cardiomyocytes, where in circMAP3K5 upregulates DAPK2 expression by targeting miR\u201022\u20103p. Moreover, we also found that miR\u201022\u20103p inhibitor and pcDNA DAPK2 could antagonize the protective effects brought by the depletion of circMAP3K5.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CircMAP3K5 is a highly conserved noncoding RNA that is upregulated during DCM process. We concluded that circMAP3K5 promotes high glucose\u2010induced cardiomyocyte apoptosis by regulating the miR\u201022\u20103p\/DAPK2 axis. The results of this study highlight a novel and translationally important circMAP3K5\u2010based therapeutic approach for DCM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.13471","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T04:42:47Z","timestamp":1695357767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>CircMAP3K5<\/scp> promotes cardiomyocyte apoptosis in diabetic cardiomyopathy by regulating <scp>miR<\/scp>\u201022\u20103p\/<scp>DAPK2<\/scp> Axis"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-9266","authenticated-orcid":false,"given":"Ming","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery The First Medical Center of PLA General Hospital  Beijing China"},{"name":"Department of Cardiology The First Hospital of Hebei Medical University  Shijiazhuang 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