MicroRNA hsa-miR-1301-3p Regulates Human ADH6, ALDH5A1 and ALDH8A1 in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway
MicroRNA hsa-miR-1301-3p Regulates Human ADH6, ALDH5A1 and ALDH8A1 in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway
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MicroRNA hsa-miR-1301-3p 调节乙醇-乙醛-乙酸代谢途径中的人 ADH6、ALDH5A1 和 ALDH8A1
DOI：
10.1124/mol.120.119693
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发表时间：
2020-08-01
影响因子：
3.6
通讯作者：
Yu, Dianke
中科院分区：
文献类型：
--
作者：
Wang, Xubing;Zhao, Yanjie;Yu, Dianke
乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）是参与多种醇类代谢的重要酶。人类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相关。microRNAs（miRNAs）作为表观遗传调节因子调节药物代谢酶的表达。为了表征人肝细胞中靶向ADH和ALDH的miRNA，我们进行了系统的生物信息学分析，以分析miRNA与ADH和ALDH转录物中的同源序列之间相互作用的自由能，然后使用公共数据库计算miRNA与其靶向ADH和ALDH基因之间的表达相关性。使用一系列生物化学测定来选择候选miRNA以评估生物信息学预测。我们的研究结果表明，11个miRNAs具有调节人类肝脏中两个ADH和七个ALDH基因表达的潜力。我们发现hsa-miR-1301- 3 p抑制了肝细胞中ADH 6、ALDH 5A 1和ALDH 8A 1的表达，并阻断了乙醇对它们的诱导。综上所述，我们的研究结果表明hsa-miR-1301- 3 p通过调节ADH和ALDH基因的表达在乙醇代谢中发挥重要作用。意义声明系统生物信息学分析表明，11个microRNA可能在人类肝脏中对2个乙醇脱氢酶（ADH）和7个乙醛脱氢酶（ALDH）基因的表达起调节作用。实验证明hsa-miR-1301- 3 p抑制了乙醇诱导的肝细胞ADH 6、ALDH 5A 1和ALDH 8A 1的表达。
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 STATEMENTSystematic 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.