Decreased mir-497-5p suppresses il-6 induced atrophy in muscle cells

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUdeA-
Autor(es): dc.contributorHarvard Medical School-
Autor(es): dc.contributorUniversal Scientific Education and Research Network (USERN)-
Autor(es): dc.contributorHarvard University-
Autor(es): dc.creatorFreire, Paula P.-
Autor(es): dc.creatorCury, Sarah S.-
Autor(es): dc.creatorLopes, Letícia O.-
Autor(es): dc.creatorFernandez, Geysson J.-
Autor(es): dc.creatorLiu, Jianming-
Autor(es): dc.creatorde Moraes, Leonardo Nazario-
Autor(es): dc.creatorde Oliveira, Grasieli-
Autor(es): dc.creatorOliveira, Jakeline S.-
Autor(es): dc.creatorde Moraes, Diogo-
Autor(es): dc.creatorCabral-Marques, Otavio-
Autor(es): dc.creatorDal-Pai-silva, Maeli-
Autor(es): dc.creatorHu, Xiaoyun-
Autor(es): dc.creatorWang, Da-Zhi-
Autor(es): dc.creatorCarvalho, Robson F.-
Data de aceite: dc.date.accessioned2025-08-21T15:56:01Z-
Data de disponibilização: dc.date.available2025-08-21T15:56:01Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cells10123527-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/231569-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/231569-
Descrição: dc.descriptionInterleukin-6 (IL-6) is a pro-inflammatory cytokine associated with skeletal muscle wasting in cancer cachexia. The control of gene expression by microRNAs (miRNAs) in muscle wasting involves the regulation of thousands of target transcripts. However, the miRNA-target networks associated with IL6-induced muscle atrophy remain to be characterized. Here, we show that IL-6 promotes the atrophy of C2C12 myotubes and changes the expression of 20 miRNAs (5 up-regulated and 15 down-regulated). Gene Ontology analysis of predicted miRNAs targets revealed posttranscriptional regulation of genes involved in cell differentiation, apoptosis, migration, and catabolic processes. Next, we performed a meta-analysis of miRNA-published data that identified miR-497-5p, a down-regulated miRNAs induced by IL-6, also down-regulated in other muscle-wasting conditions. We used miR-497-5p mimics and inhibitors to explore the function of miR-497-5p in C2C12 myoblasts and myotubes. We found that miR-497-5p can regulate the expression of the cell cycle genes CcnD2 and CcnE1 without affecting the rate of myoblast cellular proliferation. Notably, miR-497-5p mimics induced myotube atrophy and reduced Insr expression. Treatment with miR-497-5p inhibitors did not change the diameter of the myotubes but increased the expression of its target genes Insr and Igf1r. These genes are known to regulate skeletal muscle regeneration and hypertrophy via insulin-like growth factor pathway and were up-regulated in cachectic muscle samples. Our miRNA-regulated network analysis revealed a potential role for miR-497-5p during IL6-induced muscle cell atrophy and suggests that miR-497-5p is likely involved in a compensatory mechanism of muscle atrophy in response to IL-6.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University UNESP-
Descrição: dc.descriptionDepartment of Immunology Institute of Biomedical Sciences University of São Paulo-
Descrição: dc.descriptionFaculty of Medicine University of Antioquia UdeA-
Descrição: dc.descriptionDepartment of Cardiology Boston Children’s Hospital Harvard Medical School-
Descrição: dc.descriptionDepartment of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of São Paulo-
Descrição: dc.descriptionNetwork of Immunity in Infection Malignancy and Autoimmunity (NIIMA) Universal Scientific Education and Research Network (USERN)-
Descrição: dc.descriptionHarvard Stem Cell Institute Harvard University-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University UNESP-
Descrição: dc.descriptionCNPq: 141919/2016-7-
Descrição: dc.descriptionFAPESP: 2012/ 13961-6-
Descrição: dc.descriptionFAPESP: 2012/11666-7-
Descrição: dc.descriptionFAPESP: 2020/01688-0-
Descrição: dc.descriptionCNPq: 311530/2019-2-
Descrição: dc.descriptionCAPES: 88881.187095/2018-01-
Idioma: dc.languageen-
Relação: dc.relationCells-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectInflammation-
Palavras-chave: dc.subjectInterleukin-6-
Palavras-chave: dc.subjectMicroRNAs-
Palavras-chave: dc.subjectMuscle wasting-
Título: dc.titleDecreased mir-497-5p suppresses il-6 induced atrophy in muscle cells-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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