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Epigenetic modification is a mechanism associated with CH. Our study here investigated the histone demethylase KDM3C in relation to epigenetic regulation in CH. We found that KDM3C mRNA silencing alleviated CH, as evidenced by reduced ANP, BNP, and \u03b2\u2010MHC mRNAs, increased \u03b1\u2010MHC mRNA, decreased cell surface area, and reduced cellular protein\/DNA ratios. Specifically, KDM3C upregulated miR\u2010200c\u20103p expression through demethylation of H3K9me2, leading to enhanced binding of miR\u2010200c\u20103p to GAS5 and suppression of GAS5 expression; these effects then led to reduced binding of GAS5 to miR\u2010495\u20103p, increased miR\u2010495\u20103p expression, and repression of PHF8 transcription. Through these mechanisms, our data indicate that KDM3C\u2010dependent epigenetic modification promotes CH.<\/jats:p>","DOI":"10.1111\/nyas.14813","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T20:30:25Z","timestamp":1656707425000},"page":"286-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Histone demethylase KDM3C regulates the lncRNA GAS5\u2013miR\u2010495\u20103p\u2013PHF8 axis in cardiac hypertrophy"],"prefix":"10.1111","volume":"1516","author":[{"given":"Linlin","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery The Second Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-9189","authenticated-orcid":false,"given":"Naishi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0007-y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.06.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-018-9797-x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.02.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.26215"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.71"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46277"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1734819"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00539"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.535799"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194714"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.03.015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14135"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2838-3"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.07.013"},{"key":"e_1_2_10_17_1","volume-title":"Guide for the care and use of laboratory animals","author":"Garber J. 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