{"doi":"10.3389/fcvm.2021.737826","title":"microRNA-377 Signaling Modulates Anticancer Drug-Induced Cardiotoxicity in Mice","abstract":"Doxorubicin (DOX, an anthracycline) is a widely used chemotherapy agent against various forms of cancer; however, it is also known to induce dose-dependent cardiotoxicity leading to adverse complications. Investigating the underlying molecular mechanisms and strategies to limit DOX-induced cardiotoxicity might have potential clinical implications. Our previous study has shown that expression of microRNA-377 (miR-377) increases in cardiomyocytes (CMs) after cardiac ischemia-reperfusion injury in mice, but its specific role in DOX-induced cardiotoxicity has not been elucidated. In the present study, we investigated the effect of anti-miR-377 on DOX-induced cardiac cell death, remodeling, and dysfunction. We evaluated the role of miR-377 in CM apoptosis, its target analysis by RNA sequencing, and we tested the effect of AAV9-anti-miR-377 on DOX-induced cardiotoxicity and mortality. DOX administration in mice increases miR-377 expression in the myocardium. miR-377 inhibition in cardiomyocyte cell line protects against DOX-induced cell death and oxidative stress. Furthermore, RNA sequencing and Gene Ontology (GO) analysis revealed alterations in a number of cell death/survival genes. Intriguingly, we observed accelerated mortality and enhanced myocardial remodeling in the mice pretreated with AAV9-anti-miR-377 followed by DOX administration as compared to the AAV9-scrambled-control-pretreated mice. Taken together, our data suggest that in vitro miR-377 inhibition protects against DOX-induced cardiomyocyte cell death. On the contrary, in vivo administration of AAV9-anti-miR-377 increases mortality in DOX-treated mice.","journal":"Frontiers in Cardiovascular Medicine","year":2021,"id":200368,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":778038,"name":"Praveen Kumar Dubey","orcid":"0000-0002-8560-684X","position":1,"is_corresponding":false},{"id":465081,"name":"Mallikarjun Patil","orcid":"0000-0002-9238-7657","position":2,"is_corresponding":false},{"id":416639,"name":"Sarojini Singh","orcid":"0000-0001-6143-277X","position":3,"is_corresponding":false},{"id":778039,"name":"Shubham Dubey","orcid":"0000-0002-9623-7605","position":4,"is_corresponding":false},{"id":778700,"name":"Rajasekaran Namakkal Soorappan","orcid":null,"position":5,"is_corresponding":false},{"id":455437,"name":"Ramaswamy Kannappan","orcid":"0000-0001-5657-524X","position":6,"is_corresponding":false},{"id":523909,"name":"Palaniappan Sethu","orcid":"0000-0002-5794-2037","position":7,"is_corresponding":false},{"id":362101,"name":"Gangjian Qin","orcid":"0000-0002-3135-7307","position":8,"is_corresponding":false},{"id":246346,"name":"Jianyi Zhang","orcid":"0000-0002-3955-6554","position":9,"is_corresponding":false},{"id":246344,"name":"Prasanna Krishnamurthy","orcid":"0000-0002-4842-6364","position":10,"is_corresponding":false},{"id":465082,"name":"John Henderson","orcid":"0000-0001-8546-1655","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T23:50:48.624274Z","pmid":"34485421","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}