MicroRNA hsa-miR-1301-3p Regulates Human , and in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway.

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. MicroRNAs (miRNAs) function as epigenetic modulators to regulate the expression of drug-metabolizing enzymes. 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 and transcripts and then calculated expression correlations between miRNAs and their targeting and genes using a public data base. 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 two and seven genes in the human liver. We found that hsa-miR-1301-3p suppressed the expression of , , and 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 and gene expression. SIGNIFICANCE STATEMENT: Systematic bioinformatics analysis showed that 11 microRNAs might play regulatory roles in the expression of two alcohol dehydrogenase () and seven aldehyde dehydrogenase () genes in the human liver. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of , , and in liver cells and decreased their inducibility by ethanol.