{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:43:18Z","timestamp":1791585798251,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["#12\/13961-6 to RFC"],"award-info":[{"award-number":["#12\/13961-6 to RFC"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["#12\/11666-7 to PPF"],"award-info":[{"award-number":["#12\/11666-7 to PPF"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PDSE 88881.187095\/2018-01 to PPF"],"award-info":[{"award-number":["PDSE 88881.187095\/2018-01 to PPF"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["311530\/2019\u20102 to RFC"],"award-info":[{"award-number":["311530\/2019\u20102 to RFC"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["141919\/2016-7 to PPF"],"award-info":[{"award-number":["141919\/2016-7 to PPF"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin-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 post-transcriptional 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.<\/jats:p>","DOI":"10.3390\/cells10123527","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T09:34:25Z","timestamp":1639474465000},"page":"3527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Decreased miR-497-5p Suppresses IL-6 Induced Atrophy in Muscle Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0649-8279","authenticated-orcid":false,"given":"Paula P.","family":"Freire","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 Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-0933","authenticated-orcid":false,"given":"Sarah S.","family":"Cury","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University, UNESP, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-9269","authenticated-orcid":false,"given":"Let\u00edcia O.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University, UNESP, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geysson J.","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":"Faculty of Medicine, University of Antioquia, UdeA, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Nazario","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University, UNESP, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakeline S.","family":"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University, UNESP, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio","family":"Cabral-Marques","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-7714","authenticated-orcid":false,"given":"Robson F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University, UNESP, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","article-title":"Cancer cachexia: Mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon","year":"2012","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/MOG.0b013e3283347e77","article-title":"Cancer cachexia","volume":"26","author":"Tisdale","year":"2010","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1158\/1078-0432.CCR-11-2133","article-title":"Suppression of skeletal muscle turnover in cancer cachexia: Evidence from the transcriptome in sequential human muscle biopsies","volume":"18","author":"Gallagher","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1093\/annonc\/mdw420","article-title":"Perspectives of health care professionals on cancer cachexia: Results from three global surveys","volume":"27","author":"Muscaritoli","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1158\/1541-7786.MCR-13-0189","article-title":"The role of inflammatory pathways in cancer-associated cachexia and radiation resistance","volume":"11","author":"Laine","year":"2013","journal-title":"Mol. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1038\/oncsis.2016.3","article-title":"Understanding cachexia as a cancer metabolism syndrome","volume":"5","author":"Porporato","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1186\/s40064-016-2197-2","article-title":"Skeletal muscle wasting and renewal: A pivotal role of myokine IL-6","volume":"5","author":"Borges","year":"2016","journal-title":"Springerplus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168407","DOI":"10.1155\/2014\/168407","article-title":"Inflammation based regulation of cancer cachexia","volume":"2014","author":"Onesti","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/BF00364965","article-title":"Pathophysiology of cancer cachexia","volume":"1","author":"Keller","year":"1993","journal-title":"Support. Care Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C135","DOI":"10.1152\/ajpcell.00111.2012","article-title":"Rel A\/p65 is required for cytokine-induced myotube atrophy","volume":"303","author":"Yamaki","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Meyer, S.U., Sass, S., Mueller, N.S., Krebs, S., Bauersachs, S., Kaiser, S., Blum, H., Thirion, C., Krause, S., and Theis, F.J. (2015). Integrative Analysis of MicroRNA and mRNA Data Reveals an Orchestrated Function of MicroRNAs in Skeletal Myocyte Differentiation in Response to TNF-\u03b1 or IGF1. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135284"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1152\/japplphysiol.01026.2004","article-title":"IL-6-induced skeletal muscle atrophy","volume":"98","author":"Haddad","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_16","first-page":"871","article-title":"Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-\u03baB activation in response to tumor necrosis factor alpha","volume":"12","author":"Li","year":"1998","journal-title":"FASEB J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1007\/s00520-013-1878-4","article-title":"Interleukin-6 but not tumour necrosis factor-alpha predicts survival in patients with advanced cancer","volume":"21","author":"Suh","year":"2013","journal-title":"Support. Care Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/JES.0b013e3181f44f11","article-title":"Interleukin 6 as a Key Regulator of Muscle Mass during Cachexia","volume":"38","author":"Carson","year":"2010","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00000658-199101000-00005","article-title":"Elevated Circulating Interleukin-6 Is Associated with an Acute-phase Response but Reduced Fixed Hepatic Protein Synthesis in Patients with Cancer","volume":"213","author":"Fearon","year":"1991","journal-title":"Ann. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/bjc.1996.294","article-title":"The relationship between weight loss and interleukin 6 in non-small-cell lung cancer","volume":"73","author":"Scott","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1172\/JCI115767","article-title":"Evidence for the involvement of interleukin 6 in experimental cancer cachexia","volume":"89","author":"Strassmann","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1172\/JCI116816","article-title":"Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo","volume":"92","author":"Strassmann","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_23","first-page":"1353","article-title":"Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft","volume":"1","author":"Tamura","year":"1995","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/jcp.24580","article-title":"Pancreatic cancer-induced cachexia is Jak2-dependent in mice","volume":"229","author":"Gilabert","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bonetto, A., Aydogdu, T., Kunzevitzky, N., Guttridge, D.C., Khuri, S., Koniaris, L.G., and Zimmers, T.A. (2011). STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022538"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1111\/febs.12338","article-title":"Interleukin-6 myokine signaling in skeletal muscle: A double-edged sword?","volume":"280","author":"Scheele","year":"2013","journal-title":"FEBS J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"White, J.P., Baynes, J.W., Welle, S.L., Kostek, M.C., Matesic, L.E., Sato, S., and Carson, J.A. (2011). The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min\/+) mouse. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024650"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/rco2.30","article-title":"Mediators and clinical treatment for cancer cachexia: A systematic review","volume":"4","author":"Cao","year":"2021","journal-title":"JCSM Rapid Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1517\/14712598.2011.627850","article-title":"A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer","volume":"11","author":"Bayliss","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ando, K., Takahashi, F., Kato, M., Kaneko, N., Doi, T., Ohe, Y., Koizumi, F., Nishio, K., and Takahashi, K. (2014). Tocilizumab, a Proposed Therapy for the Cachexia of Interleukin6-Expressing Lung Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102436"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1182\/blood-2013-12-546374","article-title":"Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti\u2013IL-6) in multiple myeloma","volume":"123","author":"Shpilberg","year":"2014","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ejca.2011.10.014","article-title":"Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone\/prednisone versus mitoxantrone\/prednisone alone in metastatic castration-resistant prostate cancer","volume":"48","author":"Fizazi","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R296","DOI":"10.1152\/ajpregu.00147.2019","article-title":"Exercise as an anti-inflammatory therapy for cancer cachexia: A focus on interleukin-6 regulation","volume":"318","author":"Daou","year":"2020","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"730070","DOI":"10.3389\/fimmu.2021.730070","article-title":"Transcriptome Analysis of Immune Receptor Activation and Energy Metabolism Reduction as the Underlying Mechanisms in Interleukin-6-Induced Skeletal Muscle Atrophy","volume":"12","author":"Sun","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17016","DOI":"10.1073\/pnas.0708115104","article-title":"Distinctive patterns of microRNA expression in primary muscular disorders","volume":"104","author":"Eisenberg","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21909","DOI":"10.1074\/jbc.M114.561845","article-title":"Involvement of microRNAs in the regulation of muscle wasting during catabolic conditions","volume":"289","author":"Soares","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/jcsm.12168","article-title":"Small RNAome profiling from human skeletal muscle: Novel miRNAs and their targets associated with cancer cachexia","volume":"8","author":"Narasimhan","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Freire, P.P., Fernandez, G.J., Cury, S.S., de Moraes, D., Oliveira, J.S., de Oliveira, G., Dal-Pai-Silva, M., dos Reis, P.P., and Carvalho, R.F. (2019). The Pathway to Cancer Cachexia: MicroRNA-Regulated Networks in Muscle Wasting Based on Integrative Meta-Analysis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081962"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3389\/fgene.2020.00541","article-title":"MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia","volume":"11","author":"Fernandez","year":"2020","journal-title":"Front. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6998","DOI":"10.1038\/s41598-017-07236-2","article-title":"Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia","volume":"7","author":"Moraes","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/jcsm.12512","article-title":"Identification of microRNAs in skeletal muscle associated with lung cancer cachexia","volume":"11","author":"Schols","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101101","DOI":"10.1016\/j.tranon.2021.101101","article-title":"Non-coding RNAs in cancer-associated cachexia: Clinical implications and future perspectives","volume":"14","author":"Kottorou","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/ncb1101-1009","article-title":"Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K\/Akt\/mTOR and PI(3)K\/Akt\/GSK3 pathways","volume":"3","author":"Rommel","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"research0034.1","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2020","journal-title":"Genome. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D239","DOI":"10.1093\/nar\/gkv1258","article-title":"miRTarBase 2016: Updates to the experimentally validated miRNA-target interactions database","volume":"44","author":"Chou","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1093\/nar\/28.18.3442","article-title":"STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene","volume":"28","author":"Snel","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cornwell, E.W., Mirbod, A., Wu, C.-L., Kandarian, S.C., and Jackman, R.W. (2014). C26 Cancer-Induced Muscle Wasting Is IKK\u03b2-Dependent and NF-kappaB-Independent. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087776"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1152\/physiolgenomics.00128.2014","article-title":"Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia","volume":"47","author":"Shum","year":"2015","journal-title":"Physiol. Genom."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1093\/bioinformatics\/btt772","article-title":"Morpheus: A user-friendly modeling environment for multiscale and multicellular systems biology","volume":"30","author":"Brusch","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1113\/JP273097","article-title":"FoxO-dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension","volume":"595","author":"Brocca","year":"2017","journal-title":"J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Panguluri, S.K., Bhatnagar, S., Kumar, A., McCarthy, J.J., Srivastava, A.K., Cooper, N.G., Lundy, R.F., and Kumar, A. (2010). Genomic profiling of messenger RNAs and microRNAs reveals potential mechanisms of TWEAK-induced skeletal muscle wasting in mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008760"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8361237","DOI":"10.1155\/2017\/8361237","article-title":"Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle Atrophy","volume":"2017","author":"Wang","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e13278","DOI":"10.1111\/apha.13278","article-title":"miR-29c improves skeletal muscle mass and function throughout myocyte proliferation and differentiation and by repressing atrophy-related genes","volume":"226","author":"Silva","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1152\/physiolgenomics.00052.2012","article-title":"MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation","volume":"44","author":"Chen","year":"2012","journal-title":"Physiol. Genom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1242\/jcs.174235","article-title":"The NF-\u03baB-modulated microRNAs miR-195 and miR-497 inhibit myoblast proliferation by targeting Igf1r, Insr and cyclin genes","volume":"129","author":"Wei","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/SPC.0000000000000091","article-title":"Role of interleukin-6 in cachexia","volume":"8","author":"Narsale","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/MCO.0b013e32835f81b9","article-title":"MicroRNA in myogenesis and muscle atrophy","volume":"16","author":"Wang","year":"2013","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.4103\/1673-5374.189195","article-title":"miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy","volume":"11","author":"Li","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_66","first-page":"472","article-title":"Altered expression of the microRNAS and their potential target genes in the soleus muscle after peripheral denervation and reinnervation in rats","volume":"70","author":"Hsieh","year":"2011","journal-title":"J. Trauma"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/jcsm.12296","article-title":"miRNA-23a\/27a attenuates muscle atrophy and renal fibrosis through muscle-kidney crosstalk","volume":"9","author":"Zhang","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1681\/ASN.2016111213","article-title":"MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle Atrophy","volume":"28","author":"Wang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"157","DOI":"10.7150\/ijbs.17440","article-title":"Regulatory Axis of miR-195\/497 and HMGA1-Id3 Governs Muscle Cell Proliferation and Differentiation","volume":"13","author":"Qiu","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.devcel.2011.09.011","article-title":"The SCF-Fbxo40 complex induces IRS1 ubiquitination in skeletal muscle, limiting IGF1 signaling","volume":"21","author":"Shi","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1111\/febs.12253","article-title":"Mechanisms regulating skeletal muscle growth and atrophy","volume":"280","author":"Schiaffino","year":"2013","journal-title":"FEBS J."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3527\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:47:27Z","timestamp":1760168847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":72,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123527"],"URL":"https:\/\/doi.org\/10.3390\/cells10123527","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}