TNF-α Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting |
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Authors: | Tomasz Powró zek,Dominika Pigoń -Zają c,Marcin Mazurek,Michael Ochieng Otieno,Mansur Rahnama-Hezavah,Teresa Mał ecka-Massalska |
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Affiliation: | 1.Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (D.P.-Z.); (M.M.); (T.M.-M.);2.Haematological Malignancies H12O Clinical Research Unit, Spanish National Cancer Research Centre, 28029 Madrid, Spain;3.Chair and Department of Dental Surgery, Medical University of Lublin, 20-093 Lublin, Poland; |
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Abstract: | Background: Muscle atrophy is a complex catabolic condition developing under different inflammatory-related systemic diseases resulting in wasting of muscle tissue. While the knowledge of the molecular background of muscle atrophy has developed in recent years, how the atrophic conditions affect the long non-coding RNA (lncRNAs) machinery and the exact participation of the latter in the mediation of muscle loss are still unknown. The purpose of the study was to assess how inflammatory condition developing under the tumor necrosis factor alpha (TNF-α) treatment affects the lncRNAs’ expression in a mouse skeletal muscle cell line. Materials and method: A C2C12 mouse myoblast cell line was treated with TNF-α to develop atrophy, and inflammatory-related lncRNAs mediating muscle loss were identified. Bioinformatics was used to validate and analyze the discovered lncRNAs. The differences in their expression under different TNF-α concentrations and treatment times were investigated. Results: Five lncRNAs were identified in a discovery set as atrophy related and then validated. Three lncRNAs, Gm4117, Ccdc41os1, and 5830418P13Rik, were selected as being significant for inflammatory-related myotube atrophy. Dynamics changes in the expression of lncRNAs depended on both TNF-α concentration and treatment time. Bioinformatics analysis revealed the mRNA and miRNA target for selected lncRNAs and their putative involvement in the molecular processes related to muscle atrophy. Conclusions: The inflammatory condition developing in the myotube under the TNF-α treatment affects the alteration of lncRNAs’ expression pattern. Experimental and bioinformatics testing suggested the prospective role of lncRNAs in the mediation of muscle loss under an inflammatory state. |
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Keywords: | muscle atrophy, inflammation, TNF-α , lncRNA |
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