RT Journal Article SR Electronic T1 Multiple birds with one stone: microRNA hsa-miR-1301-3p regulates human ADH6, ALDH5A1 and ALDH8A1 in the ethanol-acetaldehyde-acetate metabolic pathway JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP mol.120.119693 DO 10.1124/mol.120.119693 A1 Wang, Xubing A1 Zhao, Yanjie A1 Luo, Jiao A1 Xu, Lin A1 Li, Xinmei A1 Jin, Yuan A1 Li, Chuanhai A1 Feng, Meiyao A1 Wang, Ying A1 Chen, Jing A1 Hou, Yufei A1 Zhao, Qianwen A1 Zhao, Jinquan A1 Ning, Baitang A1 Zheng, Yuxin A1 Yu, Dianke YR 2020 UL http://molpharm.aspetjournals.org/content/early/2020/06/04/mol.120.119693.abstract AB Alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) are vital enzymes involved in the metabolism of a variety of alcohols. Differences in the expression and enzymatic activity of human ADHs and ALDHs correlate with individual variability in metabolizing alcohols and drugs and in the susceptibility to alcoholic liver disease (ALD). MicroRNAs (miRNAs) function as epigenetic modulators to regulate the expression of drug metabolizing enzymes (DMEs). To characterize miRNAs that target ADHs and ALDHs in human liver cells, we carried out a systematic bioinformatics analysis to analyze free energies of the interaction between miRNAs and their cognate sequences in ADH and ALDH transcripts, and then calculated expression correlations between miRNAs and their targeting ADH and ALDH genes using a public database. Candidate miRNAs were selected to evaluate bioinformatic predictions using a series of biochemical assays. Our results showed that 11 miRNAs have the potential to modulate the expression of 2 ADH and 7 ALDH genes in the human liver. We found that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and blocked their induction by ethanol. In summary, our results revealed that hsa-miR-1301-3p plays an important role in ethanol metabolism by regulating ADH and ALDH gene expression.SIGNIFICANCE STATEMENT We showed that 11 miRNAs might play regulatory roles in the expression of 2 ADH and 7 ALDH genes in human liver via systematic bioinformatics analysis. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and blocked their induction by ethanol.