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Ischemic preconditioning (IPC) has been shown to inhibit reperfusion injury and represents an attractive model for studying cardioprotective signal transduction pathways. Long non-coding RNAs (lncRNAs) are a structurally and functionally heterogenous class of RNA transcripts with unknown roles in IPC-induced cardioprotection. Through microarray-based expression profiling of 31,423 lncRNAs in cardiac tissue from IPC mice, we identified the nuclear transcript\n                    <jats:italic>Neat1<\/jats:italic>\n                    to be rapidly and robustly decreased in response to IPC. siRNA-mediated knock down of\n                    <jats:italic>Neat1<\/jats:italic>\n                    reduced apoptosis and necrosis in murine cardiomyocytes (CM) and human iPS-derived CMs in response to prolonged hypoxia and hypoxia-reoxygenation, assessed with Annexin V\/propidium iodide-staining, a Caspase 3\/7 activity assay, LDH release, and western blot for cleaved Caspase 3. Mechanistically, Neat1 was shown to regulate processing of pro-apoptotic microRNA-22 (miR-22) in murine and human CM nuclei using a luciferase reporter assay. Hypoxia-induced downregulation of Neat1 was shown to result in accumulation of unprocessed pri-miRNA and decreased availability of biologically active miRNA, including miR-22. Addition of exogenous synthetic miR-22 reversed the protective effect of\n                    <jats:italic>Neat1<\/jats:italic>\n                    knock down in human iPS-CM. In conclusion, we have identified the nuclear lncRNA\n                    <jats:italic>Neat1<\/jats:italic>\n                    as part of a conserved oxygen-sensitive feedback mechanism by regulation of miRNA processing and a potential target in cardioprotection.\n                  <\/jats:p>","DOI":"10.1038\/s41419-020-02854-7","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T08:02:54Z","timestamp":1597996974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-3139","authenticated-orcid":false,"given":"Olof","family":"Gidl\u00f6f","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Bader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-3444","authenticated-orcid":false,"given":"Selvi","family":"Celik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Metzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Olde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Erlinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"2854_CR1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","volume":"357","author":"DM Yellon","year":"2007","unstructured":"Yellon, D. 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