Suppression of FoxO1 mRNA by β 2 ‐adrenoceptor–cAMP signaling through miR‐374b‐5p and miR‐7a‐1‐3p in C2C12 myotubes

β 2 ‐Adrenoceptor (β 2 ‐AR) signaling decreases the transcriptional activity of forkhead box O (FoxO), but the underlying mechanisms remain incompletely understood. Here, we investigated how β 2 ‐AR signaling regulates the protein abundance of FoxO and its transcriptional activity in skeletal muscle. We observed that stimulation of β 2 ‐AR with its selective agonist, clenbuterol, rapidly decreased FoxO1 mRNA expression, and this was accompanied by a decrease in either FoxO1 protein level or FoxO transcriptional activity. We subsequently observed that miR‐374b‐5p and miR‐7a‐1‐3p were rapidly upregulated in response to β 2 ‐AR stimulation. Transfection with mimics of either miRNA successfully decreased FoxO1 mRNA. Moreover, because β 2 ‐AR stimulation increased cAMP concentration, pretreatment with an adenylyl cyclase inhibitor canceled out these effects of β 2 ‐AR stimulation. These results suggest that β 2 ‐AR stimulation results in rapid upregulation of miR‐374b‐5p and miR‐7a‐1‐3p in myotubes, which in turn results in a decrease in FoxO1 mRNA expression via the β 2 ‐AR–cAMP signaling pathway.