Breed-specific expression of DROSHA, DICER and AGO2 is regulated by glucocorticoid-mediated miRNAs in the liver of newborn piglets

MicroRNA (miRNA) biogenesis is determined mainly by Drosha, Dicer and Argonaute2 (Ago2). Different breeds of pigs with vast differences in serum cortisol level demonstrate distinct profiles of hepatic miRNA expression. As yet, little is known about whether glucocorticoid contributes to the breed differences in miRNA biogenesis. Here, we used newborn Large White (LW) and Erhualian (EHL) piglets to investigate the role of glucocorticoid in breed-specific hepatic miRNA biogenesis. Erhualian piglets showing significantly higher serum cortisol level, as compared to LW, demonstrated higher hepatic expression of Drosha, Dicer and Ago2 at the protein level, but not at the mRNA level. At the post-transcriptional level, miRNAs that are predicted to target these proteins may be involved in the regulation. Hepatic expression of miR-15b and miR-222 was significantly lower in EHL piglets and was associated with higher glucocorticoid receptor binding to the respective promoter regions of miR-15b and miR-222 genes. The inhibitory effect of glucocorticoid on miR-15b and miR-222 expression was further verified in HepG2 cells, in which dexamethasone significantly downregulated the expression of primary transcripts of miR-15b and miR-222 genes. In conclusion, the higher protein content of Drosha, Dicer and Ago2 in the liver of EHL piglets is post-transcriptionally regulated, at least in part, by glucocorticoid-mediated repression of miR-15b and miR-222.