{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:17:34Z","timestamp":1792700254484,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Doxorubicin (DOX), a potent anthracycline chemotherapeutic, exhibits dose\u2010dependent cardiotoxicity that limits its clinical utility. Although miR\u2010145\u20105p demonstrates cardioprotective properties in cardiovascular diseases, its role in DOX\u2010induced cardiomyopathy remains undefined. This study investigated the therapeutic potential of miR\u2010145\u20105p against DOX\u2010induced cardiotoxicity and its underlying mechanism. Wistar rats received cumulative DOX dosing (15\u2009mg\/kg total) to establish cardiotoxicity, with miR\u2010145\u20105p overexpression achieved via adeno\u2010associated virus serotype 9 (AAV9) delivery. Cardiac function was assessed by echocardiography and serum biomarkers, including creatine kinase\u2010MB isoenzyme (CK\u2010MB), cardiac troponin T (c\u2010TnT), C\u2010reactive protein (CRP), and N\u2010terminal pro\u2010B\u2010type natriuretic peptide (NT\u2010proBNP). Histopathology (Hematoxylin &amp; Eosin\/Masson's Trichrome staining), apoptosis (TUNEL), oxidative stress (dihydroethidium staining\/malondialdehyde\/glutathione), and NLRP3 inflammasome activation (ELISA\/Western blot\/immunohistochemistry) were evaluated. Clinical relevance was determined by quantifying serum miR\u2010145\u20105p and SOX9 mRNA in healthy controls and breast cancer patients before and after DOX treatment. DOX significantly downregulated miR\u2010145\u20105p and upregulated SOX9 in rat myocardium and H9C2 cells. DOX\u2010treated patients displayed reduced serum miR\u2010145\u20105p and increased SOX9 mRNA compared with pre\u2010chemotherapy baselines. AAV9\u2010miR\u2010145\u20105p attenuated DOX\u2010induced systolic dysfunction, reduced serum biomarkers, ameliorated histopathological injury and fibrosis, suppressed apoptosis and oxidative stress, and inhibited NLRP3 inflammasome activation (decreased NLRP3, ASC, caspase\u20101, IL\u20101\u03b2, and IL\u201018). miR\u2010145\u20105p directly targeted the SOX9 3\u2032UTR, and SOX9 overexpression reversed miR\u2010145\u20105p\u2013mediated reductions in CK release, ROS production, apoptosis, and NLRP3 expression in H9C2 cells. These findings demonstrate that miR\u2010145\u20105p protects against DOX cardiotoxicity by targeting SOX9 to inhibit NLRP3 inflammasome\u2013mediated pyroptosis, offering a potential therapeutic strategy.<\/jats:p>","DOI":"10.1002\/kjm2.70126","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:27:19Z","timestamp":1763011639000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>MiR<\/scp>\n                    \u2010145\u20105p Attenuates Doxorubicin\u2010Induced Heart Injury Through Targeting Cardiomyocyte Pyroptosis"],"prefix":"10.1002","volume":"42","author":[{"given":"Xing\u2010Tao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of General Practice Wuhan Fourth Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of General Practice Wuhan Fourth Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Hua","family":"Du","sequence":"additional","affiliation":[{"name":"Department of General Practice Wuhan Fourth Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5959-2804","authenticated-orcid":false,"given":"Xiang\u2010Ping","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of General Practice Wuhan Fourth Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2023.101205"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.314681"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111702"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-030620-104842"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1385\/CT:3:2:89"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12563"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-020-09576-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.109995"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2019.01.024"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.10796"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04100-w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-2982-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.126721"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2019.01.078"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-022-00471-7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2022.078"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476278.2021.2020018"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.01.031"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000078"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-007-6052-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-014-0339-y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.25122\/jml-2021-0199"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13030568"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22393"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.10.004"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034621"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112133"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03614-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109321"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152993"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.104880"},{"issue":"9","key":"e_1_2_9_34_1","first-page":"5008","article-title":"MiR\u2010145\u20105p Alleviates Hypoxia\/Reoxygenation\u2010 Induced Cardiac Microvascular Endothelial Cell Injury in Coronary Heart Disease by Inhibiting Smad4 Expression","volume":"24","author":"Li L. 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