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An emerging property of muscle miRNAs is the cooperative regulation of transcriptional and epitranscriptional events controlling muscle phenotype. miR-155 has been related to muscular dystrophy and muscle cell atrophy. However, the function of miR-155 and its molecular targets in muscular dystrophies remain poorly understood. Through in silico and in vitro approaches, we identify distinct transcriptional profiles induced by miR-155-5p in muscle cells. The treated myotubes changed the expression of 359 genes (166 upregulated and 193 downregulated). We reanalyzed muscle transcriptomic data from dystrophin-deficient patients and detected overlap with gene expression patterns in miR-155-treated myotubes. Our analysis indicated that miR-155 regulates a set of transcripts, including Aldh1l, Nek2, Bub1b, Ramp3, Slc16a4, Plce1, Dync1i1, and Nr1h3. Enrichment analysis demonstrates 20 targets involved in metabolism, cell cycle regulation, muscle cell maintenance, and the immune system. Moreover, digital cytometry confirmed a significant increase in M2 macrophages, indicating miR-155\u2019s effects on immune response in dystrophic muscles. We highlight a critical miR-155 associated with disease-related pathways in skeletal muscle disorders.<\/jats:p>","DOI":"10.3390\/ijms25031777","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T08:44:08Z","timestamp":1706777048000},"page":"1777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Impact of miR-155-5p on Myotube Differentiation: Elucidating Molecular Targets in Skeletal Muscle Disorders"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-9269","authenticated-orcid":false,"given":"Let\u00edcia Oliveira","family":"Lopes","sequence":"first","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"},{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o 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S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grasieli","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-6236","authenticated-orcid":false,"given":"Otavio","family":"Cabral-Marques","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), S\u00e3o Paulo 05508-000, Brazil"},{"name":"Department of Medicine, Division of Molecular Medicine, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 05403-010, Brazil"},{"name":"Laboratory of Medical Investigation 29, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 05403-010, Brazil"},{"name":"Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geysson Javier","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"},{"name":"College of Medicine, University of Antioquia, UdeA, Medell\u00edn 53-108, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9521-7979","authenticated-orcid":false,"given":"Mario Hiroyuki","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Heart Institute, Center for Regenerative Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-9197","authenticated-orcid":false,"given":"Maeli","family":"Dal-Pai-Silva","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, 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