miRNA-27b levels are associated with CYP3A activity in vitro and in vivo

Previous in vitro studies have shown that microRNA-27b (miR-27b) may regulate mRNA levels of CYP3A4, vitamin D receptor (VDR), and Peroxisome proliferator-activated receptor alpha (PPAR alpha) as well as CYP3A4 protein expression and activity. In vitro studies have also shown that vitamin D may affect the expression of CYP3A4. The primary aim of this pilot study was to investigate the association between miR-27b and CYP3A expression and activity. The secondary aim was to investigate the association between 25-hydroxy vitamin D in serum and CYP3A activity. Mi-RNA-27b was quantified using real-time PCR in serum samples (n = 28) and 25-hydroxyvitamin D was measured and correlated with the levels of the endogenous CYP3A activity marker 4 beta-hydroxycholesterol. In addition, the correlation between miR-27b and CYP3A activity, measured by dextromethorphan N-demethylation and 6 beta-hydroxylation of testosterone and the gene expression of CYP3A4, VDR and PPARa were assessed in 20 human liver samples. A significant association between circulatory miR-27b levels and 4 beta-hydroxycholesterol ratio was found; P = 0.04, and between hepatic miR-27b levels and CYP3A activity, measured by dextromethorphan N-demethylation in human liver ( P = 0.04). There was no association between hepatic miR-27b and mRNA levels of CYP3A4, VDR or PPARa. There was a significant association between serum 25-hydroxyvitamin D levels and 4 beta-hydroxycholesterol ratio, P = 0.002. In conclusion, this pilotstudy supports the hypothesis that miR-27b levels as well as 25-hydroxyvitamin D may affect CYP3A activity in vivo.The results indicate that miR-27b exerts its inhibitory effect on a translational level rather than affecting mRNA levels.