Expression levels of microRNAs that are potential cytochrome P450 regulators in cynomolgus macaques

Abstract

1. Although the cynomolgus macaque is an important non-human primate species used in drug metabolism studies, cynomolgus macaque microRNA expressions have not been fully investigated.

2. The expressions of 11 cynomolgus microRNAs, all orthologues of P450 regulators in humans, were measured by quantitative polymerase chain reaction in adrenal gland, brain, heart, jejunum, kidney, liver, ovary, testis and uterus. mfa-miR-122 and mfa-miR-192, potentially important biomarkers for liver toxicity, were also analyzed.

3. Several cynomolgus microRNAs showed preferential tissue expressions: mfa-miR-1 in heart, mfa-miR-122 in liver and mfa-miR-21 and mfa-miR-192 in jejunum. The remaining nine microRNAs had more ubiquitous expressions. All 13 cynomolgus microRNAs were expressed in liver. Among the 10 animals investigated, inter-individual microRNA expression levels in liver varied from 1.5- to 5.3-fold. mfa-miR-18b was the most variable microRNA. Sex differences in expression levels were <2.0-fold, and the difference was only significant for mfa-miR-29 [1.6-fold difference (p < .05)]. Six cynomolgus microRNAs (mfa-miR-18b, mfa-miR-27a, mfa-miR-132, mfa-miR-27b, mfa-miR-122 and mfa-miR-29) were significantly correlated with P450 mRNAs: mfa-miR-18b and mfa-miR-27a were each correlated with seven P450 mRNAs.

4. Expression of these cynomolgus microRNAs in liver might indicate their possible roles in this tissue, and further investigation will clarify their involvement in P450 regulation.

Keywords:

• Cynomolgus macaque
• cytochrome P450
• drug metabolism
• microRNA

Acknowledgements

We thank members of Shin Nippon Biomedical Laboratories for their assistance with the animal experiments. The authors also greatly thank David Smallbones for copyediting a draft of this article.

Disclosure of interest

No potential conflict of interest was reported by the authors.