LncRNA IGF2AS Regulates Bovine Adipocyte Differentiation by Stabilizing the ILF3/FTO Complex and Activating PI3K/AKT Signaling.

In our previous study, we identified IGF2AS, an antisense long noncoding RNA transcript of insulin-like growth factor 2, as a critical regulator of bovine skeletal muscle development. Subsequent investigation revealed its differential expression pattern during bovine preadipocyte differentiation, though its functional significance remained unclear. Through gain- and loss-of-function experiments, we demonstrated that IGF2AS overexpression enhances adipogenic gene expression and promotes fat deposition, while its knockdown produces opposing effects. Mechanistically, RNA-seq analysis following IGF2AS silencing revealed significant downregulation of PI3K/AKT signaling pathway components. Furthermore, RNA immunoprecipitation (RIP) and co-immunoprecipitation (Co-IP) assays identified physical interactions between IGF2AS and the ILF3/FTO protein complex, suggesting a novel regulatory axis through which IGF2AS modulates PI3K/AKT-mediated adipogenesis in bovine adipocytes. These findings not only elucidate a previously unrecognized mechanism of lncRNA-mediated fat deposition regulation but also position IGF2AS as a potential molecular target for precision breeding strategies aimed at improving beef quality.