Abstract:
RNA chemical modifications are a new but rapidly developing field. They can directly affect RNA splicing, transport, stability, and translation. Consequently, they are involved in the occurrence and development of diseases that have been studied extensively in recent years. However, few studies have focused on the correlation between chemical modifications and drug effects. Here, we provide a landscape of six RNA modifications in pharmacogene RNA (pharmacoepitranscriptomics) to fully clarify the correlation between chemical modifications and drugs. We performed systematic and comprehensive analyses on pharmacoepitranscriptomics, including basic characteristics of RNA modification and modification-associated mutations and drugs affected by them. Our results show that chemical modifications are common in pharmacogenes, especially N6-methyladenosine (m6A) modification. In addition, we found a very close relationship between chemical modifications and anti-tumor drugs. More interestingly, the results demonstrate the importance of m6A modification for anti-tumor drugs, especially for drugs in triple-negative breast cancer (TNBC), ovarian cancer, and acute myelocytic leukemia (AML). These results indicate that pharmacoepitranscriptomics could be a new source of drug-effect biomarkers, especially for m6A and anti-tumor drugs.
摘要:
RNA化学修饰是一个新兴但发展迅速的领域。它们可以直接影响RNA剪接,运输,稳定性,和翻译。因此,它们参与了近年来广泛研究的疾病的发生和发展。然而,很少有研究关注化学修饰与药物作用之间的相关性。这里,我们提供了pharmacogeneRNA(pharmacoepitranscriptomics)中的6种RNA修饰,以充分阐明化学修饰与药物之间的相关性.我们对药理学进行了系统和全面的分析,包括RNA修饰和修饰相关突变的基本特征以及受其影响的药物。我们的结果表明,化学修饰在药物源很常见,特别是N6-甲基腺苷(m6A)修饰。此外,我们发现化学修饰与抗肿瘤药物之间有着非常密切的关系。更有趣的是,结果证明了m6A修饰对抗肿瘤药物的重要性,特别是对于三阴性乳腺癌(TNBC)的药物,卵巢癌,和急性粒细胞白血病(AML)。这些结果表明,药物表观转录组学可能是药物效应生物标志物的新来源,尤其是对m6A和抗肿瘤药物。