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Cardiomyocyte loss during cardiac injury, coupled with this restricted regenerative potential, represents a fundamental cause of heart failure and associated mortality. While PIWI-interacting RNAs (piRNAs) are abundantly expressed in cardiac tissue, their functional roles and molecular mechanisms in cardiomyocyte proliferation and heart regeneration remain largely undefined. In this study, we systematically investigated piRNA-mediated regulation of cardiomyocyte proliferation and cardiac repair processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using piRNA microarray analysis, we identified a novel piRNA regulating cardiomyocyte proliferation, which we named MCPPIR (myocardial cell proliferation-promoting piRNA). Genetic ablation of MCPPIR in mice attenuated cardiomyocyte proliferation and impaired neonatal heart regeneration, while MCPPIR overexpression enhanced proliferation, reduced fibrosis, and improved cardiac function post-myocardial infarction. Through mass spectrometry and RNA pull-down assays, we identified HNRNPH1 as a key binding partner. Cardiomyocyte-specific HNRNPH1 knockout mice displayed enhanced proliferative capacity. o8G-RNA immunoprecipitation sequencing revealed POC1B as the downstream target, with MCPPIR preventing HNRNPH1-mediated repression of POC1B mRNA. Mechanistically, the MCPPIR-HNRNPH1-POC1B axis maintains centrosome integrity, thereby promoting cardiomyocyte proliferation and cardiac repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals a previously unrecognized role of piRNAs in regulating cardiomyocyte proliferation. We demonstrate that MCPPIR drives cardiomyocyte proliferation and promotes cardiac repair in adult hearts through o8G-mediated post-transcriptional regulation of POC1B mRNA. These findings establish the MCPPIR\/POC1B axis as a promising therapeutic target for ischaemic heart diseases and a novel paradigm for developing regenerative therapies against myocardial injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf265","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:31:56Z","timestamp":1764592316000},"page":"270-284","source":"Crossref","is-referenced-by-count":4,"title":["MCPPIR promotes cardiomyocyte proliferation and cardiac repair via o8G oxidation of POC1B mRNA"],"prefix":"10.1093","volume":"122","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]},{"name":"Jinan Microecological Biomedicine Shandong Laboratory , Jinan 250117 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, School of Basic Medical Sciences, Soochow University , Suzhou, Jiangsu 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Heart Failure Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Institute of Chronic Diseases, The Affiliated Hospital of Qingdao University , Jiangsu Road 16, Qingdao 266021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University , Jinan 250014 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Heart Failure Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing 100037 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 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