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The present study was aimed to determine the pathologic role of MIAT in the development of DCM. MIAT knockdown was found to reduce cardiomyocyte apoptosis and improve left ventricular function in diabetic rats. High glucose could increase MIAT expression and induce apoptosis in cultured neonatal cardiomyocytes. The results of luciferase reporter assay and RNA immunoprecipitation assay revealed that MIAT was targeted by miR-22-3p in an AGO2-dependent manner. In addition, the 3\u2032-untranslated region of DAPK2 was fused to the luciferase coding region and transfected into HEK293 cells with miR-22-3p mimic, and the results showed that DAPK2 was a direct target of miR-22-3p. Our findings also indicated that MIAT overexpression could counteract the inhibitory effect of miR-22-3p on DAPK2. Moreover, MIAT knockdown was found to reduce DAPK2 expression and inhibit apoptosis in cardiomyocytes exposed to high glucose. In conclusion, our study demonstrates that MIAT may function as a competing endogenous RNA to upregulate DAPK2 expression by sponging miR-22-3p, which consequently leads to cardiomyocyte apoptosis involved in the pathogenesis of DCM.<\/jats:p>","DOI":"10.1038\/cddis.2017.321","type":"journal-article","created":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T12:43:12Z","timestamp":1499949792000},"page":"e2929-e2929","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":181,"title":["lncRNA MIAT functions as a competing endogenous RNA to upregulate DAPK2 by sponging miR-22-3p in diabetic cardiomyopathy"],"prefix":"10.1038","volume":"8","author":[{"given":"Xiang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengchao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqing","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"BFcddis2017321_CR1","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.amjmed.2008.03.046","volume":"121","author":"A Aneja","year":"2008","unstructured":"Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME . 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