Department of Pathology, College of Medicine, The Ohio State UniversityColumbus, OHUSA.
Comprehensive Cancer Center, College of Medicine, The Ohio State UniversityColumbus, OHUSA.
Gene Expr. 2021 Jun 11;20(3):179-188. doi: 10.3727/105221621X16165282414118. Epub 2021 Mar 23.
Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size from a few nucleotides to hundreds of thousands of nucleotides, which do not encode any protein. Some of these noncoding RNAs (ncRNAs) are directly or indirectly linked to the regulation of expression or functions of 25,000 proteins coded by <2% of the human genome. Among these regulatory RNAs, microRNAs are small (2125 nucleotides) RNAs that are processed from precursor RNAs that have stemloop structure, whereas noncoding RNAs >200 nucleotides are termed long noncoding RNAs (lncRNAs). Circular RNAs (circRNAs) are newly identified lncRNA members that are generated by back-splicing of primary transcripts. The functions of ncRNAs in modulating liver toxicity of xenobiotics are emerging only recently. Acetaminophen (-acetyl--aminophenol, paracetamol or APAP) is a safe analgesic and antipyretic drug at the therapeutic dose. However, it can cause severe liver toxicity that may lead to liver failure if overdosed or combined with alcohol, herbs, or other xenobiotics. This review discusses the role of ncRNAs in acetaminophen metabolism, toxicity, and liver regeneration after APAP-induced liver injury (AILI).
基因组和转录组分析已经充分证实，哺乳动物基因组的主要部分转录为不同大小的 RNA 类别，大小从几个核苷酸到几十万核苷酸不等，这些 RNA 不编码任何蛋白质。这些非编码 RNA（ncRNA）中的一些直接或间接地与 25000 个由人类基因组中<2%编码的蛋白质的表达或功能的调节有关。在这些调节 RNA 中，microRNAs 是从小的（21-25 个核苷酸）RNA 加工而来的，这些 RNA 具有茎环结构，而>200 个核苷酸的非编码 RNA 则称为长非编码 RNA（lncRNA）。Circular RNAs（circRNAs）是最近新发现的 lncRNA 成员，它们是由初级转录物的反向剪接产生的。ncRNA 在外源物肝毒性调节中的作用最近才开始显现。对乙酰氨基酚（-乙酰--氨基酚，扑热息痛或 APAP）在治疗剂量下是一种安全的镇痛药和解热药。然而，如果过量服用或与酒精、草药或其他外源性物质联合使用，它会导致严重的肝毒性，可能导致肝衰竭。这篇综述讨论了 ncRNA 在乙酰氨基酚代谢、毒性以及 APAP 诱导的肝损伤（AILI）后肝脏再生中的作用。
