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However, dilated cardiomyopathy (DCM)\u2010associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10\u00a0vs. 10) and quantitative polymerase chain reaction validation (46\u00a0vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno\u2010associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP\u2010GFP\u2010LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR\u201026a\u20105p, miR\u201030c\u20105p, miR\u2010126\u20105p and miR\u2010126\u20103p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co\u2010repressed within cardiomyocytes by these DACMs except miR\u201026a\u20105p. Delivery of a combination of miR\u201030c\u20105p, miR\u2010126\u20105p and miR\u2010126\u20103p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac\u2010specific knockout of FOXO3 (Myh6\u2010Cre\n                      <jats:sup>ERT2<\/jats:sup>\n                      , FOXO3 flox\n                      <jats:bold>\n                        <jats:sup>+\/+<\/jats:sup>\n                      <\/jats:bold>\n                      ) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating cardiac miRNA\u2010FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non\u2010invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1258","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:47:23Z","timestamp":1683164843000},"source":"Crossref","is-referenced-by-count":15,"title":["Circulating cardiac MicroRNAs safeguard against dilated cardiomyopathy"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaolei","family":"Cheng","sequence":"first","affiliation":[{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Heart Center of Henan Provincial People's Hospital Central China Fuwai Hospital of Zhengzhou University Fuwai Central China Cardiovascular Hospital and Central China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"},{"name":"Department of Anesthesiology Affiliated Drum Tower Hospital of Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Jian","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Heart Center of Henan Provincial People's Hospital Central China Fuwai Hospital of Zhengzhou University Fuwai Central China Cardiovascular Hospital and Central China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"},{"name":"Department of Biochemistry and Molecular Biology Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function School of Basic Medical Sciences Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyue","family":"Xing","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Heart Center of Henan Provincial People's Hospital Central China Fuwai Hospital of Zhengzhou University Fuwai Central China Cardiovascular Hospital and Central China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"},{"name":"Henan Key Laboratory of Chronic Disease Management Department of Health Management Center Henan Provincial People's Hospital Department of Health Management Center of Central China Fuwai Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou 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