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 ADH and ALDH transcripts and then calculated expression correlations between miRNAs and their targeting ADH and ALDH 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 ADH and seven 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: Systematic bioinformatics analysis showed that 11 microRNAs might play regulatory roles in the expression of two alcohol dehydrogenase (ADH) and seven aldehyde dehydrogenase (ALDH) genes in the human liver. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and decreased their inducibility by ethanol.

中文翻译：

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MicroRNA hsa-miR-1301-3p在乙醇-乙醛-乙酸酯代谢途径中调节人ADH6，ALDH5A1和ALDH8A1。

酒精脱氢酶（ADHs）和醛脱氢酶（ALDHs）是参与多种酒精代谢的重要酶。人ADH和ALDH的表达和酶活性的差异与代谢酒精和药物的个体差异以及对酒精性肝病的易感性有关。微小RNA（miRNA）充当表观遗传调节剂，以调节药物代谢酶的表达。为了表征靶向人肝细胞中ADH和ALDH的miRNA，我们进行了系统的生物信息学分析，以分析miRNA及其关联序列在ADH和ALDH转录物中的相互作用的自由能，然后计算miRNA及其靶向ADH和ADH之间的表达相关性。使用公共数据库的ALDH基因。使用一系列生化分析选择候选miRNA评估生物信息学预测。我们的结果表明，11种miRNA具有调节人类肝脏中2个ADH和7个ALDH基因表达的潜力。我们发现hsa-miR-1301-3p抑制了肝细胞中ADH6，ALDH5A1和ALDH8A1的表达，并阻止了乙醇的诱导。总之，我们的结果表明，hsa-miR-1301-3p通过调节ADH和ALDH基因表达在乙醇代谢中起重要作用。意义声明：系统的生物信息学分析表明，11种微RNA可能在人类肝脏中的两个乙醇脱氢酶（ADH）和七个醛脱氢酶（ALDH）基因的表达中发挥调节作用。实验证据证明，hsa-miR-1301-3p抑制了ADH6，ALDH5A1，