Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus.
Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
Toxicol Ind Health. 2020 May;36(5):386-397. doi: 10.1177/0748233720922710. Epub 2020 May 18.
Hepatocarcinogens are agents that increase the incidence of liver cancer in exposed animals or humans. It is now established that carcinogenic exposures have a widespread impact on the transcriptome, inducing both adaptive and adverse changes in the activities of genes and pathways. Chemical hepatocarcinogens have also been shown to affect expression of microRNA (miRNA), the evolutionarily conserved noncoding RNA that regulates gene expression posttranscriptionally. Considerable effort has been invested into examining the involvement of mRNA in chemical hepatocarcinogenesis and their potential usage for the classification and prediction of new chemical entities. For miRNA, there has been an increasing number of studies reported over the past decade, although not to the same degree as for transcriptomic studies. Current data suggest that it is unlikely that any gene or miRNA signature associated with short-term carcinogen exposure can replace the rodent bioassay. In this review, we discuss the application of transcriptomic and miRNA profiles to increase mechanistic understanding of chemical carcinogens and to aid in their classification.
肝癌致癌物是指能增加暴露于这些物质的动物或人体肝癌发生率的物质。目前已经证实,致癌物质暴露对转录组有广泛的影响,诱导基因和途径活性的适应性和不利变化。化学肝癌致癌物也已被证明会影响 microRNA(miRNA)的表达,miRNA 是一种进化上保守的非编码 RNA,可在后转录水平调节基因表达。人们已经投入了大量的精力来研究 mRNA 在化学性肝癌发生中的作用及其在新化学物质的分类和预测中的潜在用途。在过去的十年中,miRNA 的研究报告数量不断增加,尽管不如转录组研究那么多。目前的数据表明,与短期致癌物暴露相关的任何基因或 miRNA 特征都不太可能替代啮齿动物生物测定。在这篇综述中,我们讨论了转录组和 miRNA 谱的应用,以增加对化学致癌物的机制理解,并有助于对其进行分类。