Temporal dynamics and functional implications of MiRNAs in denervation-induced skeletal muscle atrophy

Peripheral nerve injury often leads to muscle atrophy and compromised functional recovery. Growing evidence underscores the critical role of microRNAs (miRNAs) as key epigenetic regulators in this degenerative process. However, most current studies are limited to isolated time points, leaving a gap in the systematic understanding of the temporal dynamics of miRNA expression and their regulatory networks during the initiation of muscle atrophy.

In this study, we employed small RNA sequencing to dynamically profile miRNA expression in the tibialis anterior muscle across a time series from 12 h to 28 days following denervation. Through differential expression analysis, functional enrichment, and construction of miRNA-mRNA interaction networks integrated with multi-dimensional bioinformatics approaches including GO and KEGG analyses, we identified 199 temporally differentially expressed miRNAs. A pronounced shift in miRNA expression was observed at day 3 post-injury. Functional annotation of target genes revealed an transition in regulatory emphasis from cytoskeletal remodeling toward energy metabolic imbalance. Within this core window of day 3, rno-miR-128-1-5p was found to regulate mitochondrial metabolism-related genes, and cooperated with rno-miR-296-3p in modulating tight junction pathways.

Our findings illustrate that a time-specific molecular regulatory network underpins the pathological progression of denervation-induced muscle atrophy. These insights offer novel targets for developing precise therapeutic strategies aligned with disease timeline.