{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:08:24Z","timestamp":1760144904027,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["GI\/5"],"award-info":[{"award-number":["GI\/5"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Muscular atrophy is a complex catabolic condition that develops due to several inflammatory-related disorders, resulting in muscle loss. Tumor necrosis factor alpha (TNF-\u03b1) is believed to be one of the leading factors that drive inflammatory response and its progression. Until now, the link between inflammation and muscle wasting has been thoroughly investigated, and the non-coding RNA machinery is a potential connection between the candidates. This study aimed to identify specific miRNAs for muscular atrophy induced by TNF-\u03b1 in the C2C12 murine myotube model. The difference in expression of fourteen known miRNAs and two newly identified miRNAs was recorded by next-generation sequencing between normal muscle cells and treated myotubes. After validation, we confirmed the difference in the expression of one novel murine miRNA (nov-mmu-miRNA-1) under different TNF-\u03b1-inducing conditions. Functional bioinformatic analyses of nov-mmu-miRNA-1 revealed the potential association with inflammation and muscle atrophy. Our results suggest that nov-mmu-miRNA-1 may trigger inflammation and muscle wasting by the downregulation of LIN28A\/B, an anti-inflammatory factor in the let-7 family. Therefore, TNF-\u03b1 is involved in muscle atrophy through the modulation of the miRNA cellular machinery. Here, we describe for the first time and propose a mechanism for the newly discovered miRNA, nov-mmu-miRNA-1, which may regulate inflammation and promote muscle atrophy.<\/jats:p>","DOI":"10.3390\/ijms25116064","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:35:32Z","timestamp":1717137332000},"page":"6064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Undiscovered miRNA Involved in Tumor Necrosis Factor Alpha-Induced Atrophy in Mouse Skeletal Muscle Cell Line"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-3237","authenticated-orcid":false,"given":"Dominika","family":"Pigo\u0144-Zaj\u0105c","sequence":"first","affiliation":[{"name":"Department of Human Physiology of the Chair of Preclinical Sciences, Medical University in Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4040-0450","authenticated-orcid":false,"given":"Marcin","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Department of Human Physiology of the Chair of Preclinical Sciences, Medical University in Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2805-6755","authenticated-orcid":false,"given":"Miros\u0142aw","family":"Maziarz","sequence":"additional","affiliation":[{"name":"Department of Human Physiology of the Chair of Preclinical Sciences, Medical University in Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ochieng\u2019 Otieno","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, Oncohealth Institute, Fundacion Jim\u00e9nez D\u00edaz University Hospital, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9007-828X","authenticated-orcid":false,"given":"Javier","family":"Martinez-Useros","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, Oncohealth Institute, Fundacion Jim\u00e9nez D\u00edaz University Hospital, 28040 Madrid, Spain"},{"name":"Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3384-0324","authenticated-orcid":false,"given":"Teresa","family":"Ma\u0142ecka-Massalska","sequence":"additional","affiliation":[{"name":"Department of Human Physiology of the Chair of Preclinical Sciences, Medical University in Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-8548","authenticated-orcid":false,"given":"Tomasz","family":"Powr\u00f3zek","sequence":"additional","affiliation":[{"name":"Department of Human Physiology of the Chair of Preclinical Sciences, Medical University in Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110463","DOI":"10.1016\/j.cellsig.2022.110463","article-title":"Near-infrared light-triggered polypyrrole promotes C2C12 cell differentiation and inhibits TNF-\u03b1 induced myotube atrophy","volume":"100","author":"Wu","year":"2022","journal-title":"Cell. Signal."},{"doi-asserted-by":"crossref","unstructured":"Hitachi, K., Honda, M., and Tsuchida, K. (2022). The Functional Role of Long Non-Coding RNA in Myogenesis and Skeletal Muscle Atrophy. Cells, 11.","key":"ref_2","DOI":"10.3390\/cells11152291"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.3389\/fphys.2019.01298","article-title":"Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1462","DOI":"10.1002\/wsbm.1462","article-title":"Skeletal muscle: A review of molecular structure and function, in health and disease","volume":"12","author":"Mukund","year":"2020","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.3892\/mmr.2021.12125","article-title":"Pyropia yezoensis protein protects against TNF-\u03b1-induced myotube atrophy in C2C12 myotubes via the NF-\u03baB signaling pathway","volume":"24","author":"LEE","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3390\/muscles1020012","article-title":"Myogenetic Oligodeoxynucleotide Restores Differentiation and Reverses Inflammation of Myoblasts Aggravated by Cancer-Conditioned Medium","volume":"1","author":"Nihashi","year":"2022","journal-title":"Muscles"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105807","DOI":"10.1016\/j.phrs.2021.105807","article-title":"Skeletal muscle atrophy: From mechanisms to treatments","volume":"172","author":"Yin","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"597675","DOI":"10.3389\/fphys.2020.597675","article-title":"Inflammation and Skeletal Muscle Wasting during Cachexia","volume":"11","author":"Webster","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.omtn.2021.10.010","article-title":"Non-coding RNA basis of muscle atrophy","volume":"26","author":"Liu","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"577010","DOI":"10.3389\/fcell.2020.577010","article-title":"Regulation of Skeletal Muscle Atrophy in Cachexia by MicroRNAs and Long Non-coding RNAs","volume":"8","author":"Chen","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115517","DOI":"10.1016\/j.biopha.2023.115517","article-title":"Advances in research on cell models for skeletal muscle atrophy","volume":"167","author":"Li","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12964-015-0083-0","article-title":"TNF-\u03b1 and IGF1 modify the microRNA signature in skeletal muscle cell differentiation","volume":"13","author":"Meyer","year":"2015","journal-title":"Cell Commun. Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1302\/2046-3758.911.BJR-2020-0178.R1","article-title":"Role of microRNA in muscle regeneration and diseases related to muscle dysfunction in atrophy, cachexia, osteoporosis, and osteoarthritis","volume":"9","author":"Hamilton","year":"2020","journal-title":"Bone Jt. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1093\/ndt\/gfz193","article-title":"Skeletal muscle wasting in chronic kidney disease: The emerging role of microRNAs","volume":"35","author":"Robinson","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"unstructured":"(2024, January 12). Available online: https:\/\/www.ebi.ac.uk\/gxa\/help\/index.html.","key":"ref_15"},{"doi-asserted-by":"crossref","unstructured":"Ma, Y., Shen, N., Wicha, M.S., and Luo, M. (2021). The roles of the let-7 family of micrornas in the regulation of cancer stemness. Cells, 10.","key":"ref_16","DOI":"10.3390\/cells10092415"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-065X.2011.01089.x","article-title":"MicroRNAs, new effectors and regulators of NF-\u03baB","volume":"246","author":"Boldin","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.imbio.2011.08.005","article-title":"Expression of let-7i is associated with Toll-like receptor 4 signal in coronary artery disease: Effect of statins on let-7i and Toll-like receptor 4 signal","volume":"217","author":"Satoh","year":"2012","journal-title":"Immunobiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2009.10.014","article-title":"An Epigenetic Switch Involving NF-\u03baB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation","volume":"139","author":"Iliopoulos","year":"2009","journal-title":"Cell"},{"doi-asserted-by":"crossref","unstructured":"Ji, Y., Li, M., Chang, M., Liu, R., Qiu, J., Wang, K., Deng, C., Shen, Y., Zhu, J., and Wang, W. (2022). Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants, 11.","key":"ref_20","DOI":"10.3390\/antiox11091686"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1111\/asj.13224","article-title":"Effect of dietary fish oil intake on ubiquitin ligase expression during muscle atrophy induced by sciatic nerve denervation in mice","volume":"90","author":"Komiya","year":"2019","journal-title":"Anim. Sci. J."},{"doi-asserted-by":"crossref","unstructured":"Xiao, J. (2018). Muscle Atrophy, Springer.","key":"ref_22","DOI":"10.1007\/978-981-13-1435-3"},{"doi-asserted-by":"crossref","unstructured":"Gan, M., Ma, J., Chen, J., Chen, L., Zhang, S., Zhao, Y., Niu, L., Li, X., Zhu, L., and Shen, L. (2022). miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy. Nutrients, 14.","key":"ref_23","DOI":"10.3390\/nu14091861"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.celrep.2015.07.066","article-title":"TNF-\u03b1-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy","volume":"12","author":"Fiorillo","year":"2015","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1752-8062.2010.00199.x","article-title":"The RNA editor gene ADAR1 is induced in myoblasts by inflammatory ligands and buffers stress response","volume":"3","author":"Meltzer","year":"2010","journal-title":"Clin. Transl. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/art.41215","article-title":"Muscle Weakness in Myositis: MicroRNA-Mediated Dystrophin Reduction in a Myositis Mouse Model and Human Muscle Biopsies","volume":"72","author":"Kinder","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1101\/gr.139105.112","article-title":"Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors","volume":"22","author":"Wang","year":"2012","journal-title":"Genome Res."},{"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.","key":"ref_28","DOI":"10.1371\/journal.pone.0008760"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1010428317714624","DOI":"10.1177\/1010428317714624","article-title":"TWEAK\/Fn14 signaling in tumors","volume":"39","author":"Hu","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biocel.2013.12.003","article-title":"Myostatin signaling regulates Akt activity via the regulation of miR-486 expression","volume":"47","author":"Hitachi","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.arr.2015.08.007","article-title":"MicroRNAs: Modulators of the underlying pathophysiology of sarcopenia?","volume":"24","author":"Brown","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3389\/fphys.2017.00788","article-title":"mTOR as a key regulator in maintaining skeletal muscle mass","volume":"8","author":"Yoon","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1166\/jbn.2023.3745","article-title":"Biological Function of Rab11-Family Interacting Protein 4 in the Development of Preeclampsia and Their Underlying Mechanism","volume":"19","author":"Yang","year":"2023","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_34","first-page":"5093","article-title":"Rab11 Functions as an Oncoprotein via Nuclear Factor kappa B (NF-\u03baB) Signaling Pathway in Human Bladder Carcinoma","volume":"24","author":"Gong","year":"2018","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"doi-asserted-by":"crossref","unstructured":"Sun, X., Wang, X., Chen, T., Li, T., Cao, K., Lu, A., Chen, Y., Sun, D., Luo, J., and Fan, J. (2010). Myelin activates FAK\/Akt\/NF-\u03baB pathways and provokes CR3-dependent inflammatory response in murine system. PLoS ONE, 5.","key":"ref_35","DOI":"10.1371\/journal.pone.0009380"},{"doi-asserted-by":"crossref","unstructured":"Alvarez, A.M., DeOcesano-Pereira, C., Teixeira, C., and Moreira, V. (2020). IL-1\u03b2 and TNF-\u03b1 Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved. Cells, 9.","key":"ref_36","DOI":"10.3390\/cells9092005"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2796.2010.02334.x","article-title":"Can muscle regeneration fail in chronic inflammation: A weakness in inflammatory myopathies?","volume":"269","author":"Loell","year":"2011","journal-title":"J. Intern. Med."},{"doi-asserted-by":"crossref","unstructured":"Otis, J.S., Niccoli, S., Hawdon, N., Sarvas, J.L., Frye, M.A., Chicco, A.J., and Lees, S.J. (2014). Pro-inflammatory mediation of myoblast proliferation. PLoS ONE, 9.","key":"ref_39","DOI":"10.1371\/journal.pone.0092363"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"791363","DOI":"10.3389\/fendo.2021.791363","article-title":"Let-7e-5p Regulates IGF2BP2, and Induces Muscle Atrophy","volume":"12","author":"Okamura","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/age.12272","article-title":"Altered microRNA expression in bovine skeletal muscle with age","volume":"46","author":"Sun","year":"2015","journal-title":"Anim. Genet."},{"doi-asserted-by":"crossref","unstructured":"Powr\u00f3zek, T., Pigo\u0144-Zajac, D., Mazurek, M., Otieno, M.O., Rahnama-Hezavah, M., and Ma\u0142ecka-Massalska, T. (2022). TNF-\u03b1 Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting. Int. J. Mol. Sci., 23.","key":"ref_42","DOI":"10.3390\/ijms23073878"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:51:41Z","timestamp":1760107901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25116064"],"URL":"https:\/\/doi.org\/10.3390\/ijms25116064","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,5,31]]}}}