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Although lncRNA HOTTIP has been identified to play an important role in coronary artery diseases, its role and specific mechanism in AMI remain unclear. To investigate the potential role of HOTTIP in MI, HOTTIP expression in hypoxia-treated cardiomyocytes and myocardial tissues of MI mice was evaluated. The potential targets of HOTTIP and miR-92a-2 were predicted using Starbase and Targetscan. To further determine the cardio-protective effects of HOTTIP in vivo, si-HOTTIP and miR-92a-2 mimics were individually or co-injected into mice through intramyocardial injection. Moreover, their roles were further confirmed in rescue experiments. HOTTIP was significantly upregulated in ischemic myocardium of MI mice and hypoxia-induced cardiomyocytes. Moreover, HOTTIP knockdown markedly promoted cardiomyocyte growth and inhibited cardiomyocyte apoptosis in vitro. Luciferase reporter assay showed that HOTTIP could directly sponge miR-92a-2 to negatively regulate miR-92a-2 expression. In addition, c-Met was identified as a direct target of miR-92a-2, and their correlation was confirmed by luciferase reporter assay. MiR-92a-2 overexpression significantly enhanced the protective effect of HOTTIP knockdown against AMI through partially inhibiting c-Met expression. Our results demonstrated that HOTTIP downregulation attenuated AMI progression via the targeting miR-92a-2\/c-Met axis and suggested that HOTTIP might be a potential therapeutic target for AMI.<\/jats:p>","DOI":"10.1007\/s12012-021-09717-3","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T12:03:11Z","timestamp":1642593791000},"page":"352-364","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["LncRNA HOTTIP Knockdown Attenuates Acute Myocardial Infarction via Regulating miR-92a-2\/c-Met Axis"],"prefix":"10.1007","volume":"22","author":[{"given":"Beilei","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Likun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"issue":"10065","key":"9717_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0140-6736(16)30677-8","volume":"389","author":"GW Reed","year":"2017","unstructured":"Reed, G. 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