Huang Kexin, Wu Sijia, Yang Xiaotong, Wang Tiangang, Liu Xi, Zhou Xiaobo, Huang Liyu
School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, P.R. China.
West China Biomedical Big Data Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
NAR Cancer. 2023 Jan 23;5(1):zcad004. doi: 10.1093/narcan/zcad004. eCollection 2023 Mar.
Alternative polyadenylation (APA) is a widespread posttranscriptional regulation process. APA generates diverse mRNA isoforms with different 3' UTR lengths, affecting mRNA expression, miRNA binding regulation and alternative splicing events. Previous studies have demonstrated the important roles of APA in tumorigenesis and cancer progression through diverse aspects. Thus, a comprehensive functional landscape of diverse APA events would aid in a better understanding of the underlying mechanisms related to APA in human cancers. Here, we built CAFuncAPA (https://relab.xidian.edu.cn/CAFuncAPA/) to systematically annotate the functions of 15478 APA events in human pan-cancers. Specifically, we first identified APA events associated with cancer survival and tumor progression. We annotated the potential downstream effects of APA on genes/isoforms expression, regulation of miRNAs, RNA binding proteins (RBPs) and alternative splicing events. Moreover, we also identified up-regulators of APA events, including the effects of genetic variants on poly(A) sites and RBPs, as well as the effect of methylation phenotypes on APA events. These findings suggested that CAFuncAPA can be a helpful resource for a better understanding of APA regulators and potential functions in cancer biology.
可变聚腺苷酸化(APA)是一种广泛存在的转录后调控过程。APA产生具有不同3'UTR长度的多种mRNA异构体,影响mRNA表达、miRNA结合调控和可变剪接事件。先前的研究已经从多个方面证明了APA在肿瘤发生和癌症进展中的重要作用。因此,全面了解不同APA事件的功能格局将有助于更好地理解人类癌症中与APA相关的潜在机制。在这里,我们构建了CAFuncAPA(https://relab.xidian.edu.cn/CAFuncAPA/)来系统注释人类泛癌中15478个APA事件的功能。具体而言,我们首先确定了与癌症生存和肿瘤进展相关的APA事件。我们注释了APA对基因/异构体表达、miRNA调控、RNA结合蛋白(RBP)和可变剪接事件的潜在下游影响。此外,我们还确定了APA事件的上调因子,包括遗传变异对聚腺苷酸化位点和RBP的影响,以及甲基化表型对APA事件的影响。这些发现表明,CAFuncAPA可以成为更好地理解癌症生物学中APA调控因子和潜在功能的有用资源。