Characterization of Undiscovered miRNA Involved in Tumor Necrosis Factor Alpha-Induced Atrophy in Mouse Skeletal Muscle Cell Line.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Tumor Necrosis Factor-alpha*/metabolism ; Tumor Necrosis Factor-alpha*/genetics ; Muscular Atrophy*/genetics ; Muscular Atrophy*/metabolism ; Muscular Atrophy*/pathology ; Muscular Atrophy*/chemically induced; Animals ; Mice ; Cell Line ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/pathology ; Muscle Fibers, Skeletal/drug effects ; Gene Expression Regulation/drug effects ; High-Throughput Nucleotide Sequencing

Muscular atrophy is a complex catabolic condition that develops due to several inflammatory-related disorders, resulting in muscle loss. Tumor necrosis factor alpha (TNF-α) 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-α 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-α-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-α 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.

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GI/5 Medical University of Lublin

Keywords: TNF-α; inflammation; miRNA; muscle atrophy; myotubes

0 (MicroRNAs)
0 (Tumor Necrosis Factor-alpha)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240703

20240703

PMC11172509

10.3390/ijms25116064

38892252