{"corpus_id":208329476,"paper_sha":"270a5592a697390de3baf9e524af264d43b62b1a","doi":"10.1186/s11658-019-0186-5","arxiv_id":null,"pmid":31798643,"pmcid":"6882197","mag_id":2990659715,"dblp_id":null,"acl_id":null,"title":"MicroRNA-146a protects against myocardial ischaemia reperfusion injury by targeting Med1","year":2019,"publication_date":"2019-11-27","venue":"Cellular & Molecular Biology Letters","journal":{"name":"Cellular & Molecular Biology Letters","pages":null,"volume":"24"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":33,"citation_count":24,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Apoptosis","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D017209"},{"d":"Caspase 3","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D053148"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Gene Expression Profiling","mj":false,"ui":"D020869"},{"d":"Gene Expression Regulation","mj":false,"ui":"D005786"},{"d":"Heart Function Tests","mj":false,"ui":"D006334"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mediator Complex Subunit 1","mj":false,"qs":[{"q":"antagonists & inhibitors","mj":false,"ui":"Q000037"},{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D056913"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Knockout","mj":false,"ui":"D018345"},{"d":"MicroRNAs","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D035683"},{"d":"Myocardial Infarction","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D009203"},{"d":"Myocardial Reperfusion Injury","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D015428"},{"d":"Myocardium","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D009206"},{"d":"Myocytes, Cardiac","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D032383"},{"d":"Oligonucleotide Array Sequence Analysis","mj":false,"ui":"D020411"},{"d":"Proto-Oncogene Proteins c-bcl-2","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D019253"},{"d":"RNA, Small Interfering","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D034741"},{"d":"Signal Transduction","mj":false,"ui":"D015398"},{"d":"bcl-2-Associated X Protein","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051028"}],"chemicals":[{"n":"Bax protein, mouse","ui":"C494827","reg":"0"},{"n":"Med1 protein, mouse","ui":"C538856","reg":"0"},{"n":"Mediator Complex Subunit 1","ui":"D056913","reg":"0"},{"n":"MicroRNAs","ui":"D035683","reg":"0"},{"n":"Mirn146 microRNA, mouse","ui":"C534190","reg":"0"},{"n":"Proto-Oncogene Proteins c-bcl-2","ui":"D019253","reg":"0"},{"n":"RNA, Small Interfering","ui":"D034741","reg":"0"},{"n":"bcl-2-Associated X Protein","ui":"D051028","reg":"0"},{"n":"Bcl2 protein, mouse","ui":"C052617","reg":"114100-40-2"},{"n":"Casp3 protein, mouse","ui":"C505409","reg":"EC 3.4.22.-"},{"n":"Caspase 3","ui":"D053148","reg":"EC 3.4.22.-"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://cmbl.biomedcentral.com/track/pdf/10.1186/s11658-019-0186-5","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/270a5592a697390de3baf9e524af264d43b62b1a","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Myocardial ischaemia reperfusion injury (MIRI) is a difficult problem in clinical practice, and it may involve various microRNAs. This study investigated the role that endogenous microRNA-146a plays in myocardial ischaemia reperfusion and explored the possible target genes. MIRI models were established in microRNA-146a deficient (KO) and wild type (WT) mice. MicroRNA-146a expression was evaluated in the myocardium of WT mice after reperfusion. The heart function, area of myocardium infarction and in situ apoptosis were compared between the KO and WT mice. Microarray was used to explore possible target genes of microRNA-146a, while qRT-PCR and dual luciferase reporter assays were used for verification. Western blotting was performed to detect the expression levels of the target gene and related signalling molecules. A rescue study was used for further testing. MicroRNA-146a was upregulated 1 h after reperfusion. MicroRNA-146a deficiency decreased heart function and increased myocardial infarction and apoptosis. Microarray detected 19 apoptosis genes upregulated in the KO mice compared with the WT mice. qRT-PCR and dual luciferase verified that Med1 was one target gene of microRNA-146a. TRAP220, encoded by Med1 in the KO mice, was upregulated, accompanied by an amplified ratio of Bax/Bcl2 and increased cleaved caspase-3. Inhibition of microRNA-146a in H9C2 cells caused increased TRAP220 expression and more apoptosis under the stimulus of hypoxia and re-oxygenation, while knockdown of the increased TRAP220 expression led to decreased cell apoptosis. MicroRNA-146a exerts a protective effect against MIRI, which might be partially mediated by the target gene Med1 and related to the apoptosis signalling pathway.","claims":[{"public_id":"cl_d2b00f7c689904388fe6592f2dd31c79","status":"active","text":"Knockdown of increased TRAP220 expression in H9C2 cells under hypoxia and re-oxygenation decreased cell apoptosis.","confidence":0.9,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":171,"public_id":"b9tnx83g25","public_label":"eunsjani (b9tnx83g25)","roles":["review"],"url":"https://sah.borca.ai/u/b9tnx83g25"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_d2b00f7c689904388fe6592f2dd31c79"},{"public_id":"cl_2398a24f77cd5dc89a63f10d25ff248e","status":"active","text":"Med1 is a target gene of microRNA-146a, 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