近日，卫生毒理学研究团队在酒精代谢酶调控机制领域取得重要进展。相关研究成果以“A novel mechanism underlying alcohol dehydrogenase expression: hsa-miR-148a-3p promotes ADH4 expression via an AGO1-dependent manner in control and ethanol-exposed hepatic cells”为题，在线发表在期刊Biochemical Pharmacology（IF=4.96，药学1区，DOI: 10.1016/j.bcp.2021.114458）上。
Alcohol drinking is very popular in many cultural, religious and social practices. However, chronic and excess alcohol drinking has various detrimental effects on human health, including alcoholic hepatitis (AH), the most severe form of alcoholic liver disease. Global status report on alcohol and health (2018) released by World Health Organization (WHO) points out that mortality resulting from harmful use of alcohol is higher than that caused by other diseases such as AIDS, tuberculosis, and diabetes, with about 3 million deaths in 2016. To date, alcohol abuse is a growing burden worldwide and poses a big threat to global public health. While the effects of alcohol on liver injury have been clearly documented, mechanisms underlying the expressions of alcohol-metabolizing genes are currently limited. Principally, alcohol is oxidized to acetaldehyde in hepatic cells by alcohol dehydrogenase (ADH), and acetaldehyde is converted to acetate by aldehyde dehydrogenase (ALDH). It is now known that the expression or activity imbalance between ADH and ALDH is a critical factor contributing to alcoholism development and alcohol-related tissue damage.
In the present study, we showed miR-148a promoted ADH4 expression by directly binding to the coding sequence of ADH4 and increasing the mRNA stability via an AGO1-dependent manner. The non-canonical positive regulation of miR-148a on ADH4 revealed a new regulationary mechanism for ADH genes and provided new clues to elucidate the epigenetic regulationary mechanism of ADH genes.
Dr. Dianke Yu is the corresponding author of the paper. Dr. Jiao Luo and postgraduate students Yufei Hou are the co-first authors. This work was supported by grants from the National Natural Science Foundation of China (81903354, 91943301, and 91743113),China Postdoctoral Science Foundation (2020M672008), National Key R&D Program of China (2017YFC1600201), Postdoctoral Innovation Project of Shandong Province, and the Qingdao Postdoctoral Application Research Project.