Bta-Novel-miR-357 Inhibits the Proliferation and Promotes Apoptosis of Bovine Myoblasts by Targeting S100A2

The unresolved mechanisms underlying heterosis in beef cattle production traits hinder the optimization of crossbreeding strategies. In this study, we generated Wagyu × Hereford hybrid cattle (F1) and observed significantly enhanced growth rates compared to purebred Hereford controls, prompting further investigation into the epigenetic regulatory basis of heterosis in bovine muscle development. Combined microRNA-seq and RNA-seq profiling of the longissimus dorsi muscle identified 17 differentially expressed miRNAs and 489 differentially expressed genes (DEGs), enabling the construction of a comprehensive miRNA-mRNA regulatory network. Notably, decreased expression of bta-novel-miR-357 (novel-miR-357) and increased expression of S100A2 (S100 Calcium-Binding Protein A2) mRNA were observed in the hybrid cattle. Functional assays in primary bovine myoblasts demonstrated that novel-miR-357 and siS100A2 inhibited cell proliferation and promoted apoptosis. Dual-luciferase reporter assays confirmed that novel-miR-357 directly binds to the 3'UTR of S100A2 mRNA, establishing a targeted regulatory relationship. Furthermore, novel-miR-357 was shown to inhibit proliferation and promote apoptosis of bovine myoblasts through targeting S100A2 mRNA. These findings reveal a novel epigenetic regulatory axis (novel-miR-357/S100A2 mRNA) involved in early muscle development and provide an important molecular mechanism for deeper understanding of the epigenetic regulatory processes underlying heterosis in cattle. Nevertheless, given the polygenic complexity of heterosis, it is important to recognize that this pathway likely represents only one of several contributing factors to this complex trait.