Transcriptomic study reveals partial pathway rescue and distinct microRNA networks in dystrophic pigs, highlighting novel therapeutic targets for muscular dystrophy.
Key Points
To delineate global transcriptional alterations and condition-specific microRNA–mRNA regulatory networks in tailored porcine models of Duchenne and Becker muscular dystrophies.
Analyzed triceps brachii muscle from 4 DMD (DMDΔ52), 4 BMD (DMDΔ51-52), and 5 wild-type pigs at 3.5 months of age using stranded total RNA-seq and small RNA-seq.
Identified differentially expressed mRNAs (|log2FC| ≥ 1, adjusted p ≤ 0.05) and miRNAs (adjusted p ≤ 0.05) using DESeq2.
Predicted functional miRNA–mRNA regulatory networks using RNAhybrid (MFE < -25 kcal/mol, seed pairing) filtered by inverse Pearson correlation.
DMD muscle demonstrated 1,440 upregulated genes (enriched for inflammatory and innate immune pathways) and 487 downregulated genes (enriched for contractile, structural, and calcium-handling machinery) relative to wild type, whereas BMD muscle showed partial restoration toward wild-type expression.
Differential expression revealed 22 upregulated and 12 downregulated miRNAs in DMD versus wild type, alongside 36 upregulated and 21 downregulated miRNAs in BMD versus wild type.
Identified disease-specific biomarker candidates, including ssc-miR-296-3p (exclusively elevated in DMD, targeting 228 structural and metabolic genes) and ssc-miR-423-5p (specifically elevated in BMD, targeting 67 calcium and developmental genes).