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Long noncoding RNA (lncRNA) metastasis\u2010associated lung adenocarcinoma transcript 1 (MALAT1) has been previously demonstrated to regulate the proliferation and metastasis of several tumors. However, little is known about the effects of MALAT1 in MI and in regulating the cell date after MI. In our study, first, it was shown that the expression levels of MALAT1 were increased in the MI samples compared with normal tissues using quantitative reverse\u2010transcription polymerase chain reaction. Then, MALAT1 knockdown could significantly decrease the cell viability and increase the apoptotic rates in isoproterenol (ISO)\u2010treated H9C2 cells. In addition, we screened the possible target and found that miR\u2010558 is its direct target using dual luciferase reporter assay, indicating that MALAT1 functioned as decoys sponging miR\u2010558. Transfection of miR\u2010558 mimic decreased the cell viability and enhanced the apoptosis. Furthermore, we revealed that miR\u2010558 could downregulate ULK1 expression and suppressed ISO\u2010induced protective autophagy. Activation of MALAT1\/miR\u2010558\/ULK1 pathway protected H9C2 cells from ISO\u2010induced mitochondria\u2010dependent apoptosis. Finally, we used MALAT1\u2010knockout mice to further demonstrated that MALAT1 protected cardiomyocytes from apoptosis and partially improved the cardiac functions upon ISO treatment. In conclusion, we elucidated that lncRNA MALAT1 protected cardiomyocytes from ISO\u2010induced apoptosis by sponging miR\u2010558 thus promoting ULK1\u2010dependent autophagy. Targeting lncRNA MALAT1 might become a potential strategy in protecting cardiomyocytes during MI.<\/jats:p>","DOI":"10.1002\/jcp.27925","type":"journal-article","created":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T05:28:24Z","timestamp":1544246904000},"page":"10842-10854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["LncRNA MALAT1 protects cardiomyocytes from isoproterenol\u2010induced apoptosis through sponging miR\u2010558 to enhance ULK1\u2010mediated protective autophagy"],"prefix":"10.1002","volume":"234","author":[{"given":"Xiaoyan","family":"Guo","sequence":"first","affiliation":[{"name":"Henan Province People's Hospital, People's Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital Zhengzhou, Henan  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Henan Province People's 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