CAFuncAPA: a knowledgebase for systematic functional annotations of APA events in human cancers.

NAR Cancer Pub Date : 2023-01-23 eCollection Date: 2023-03-01 DOI:10.1093/narcan/zcad004
Kexin Huang, Sijia Wu, Xiaotong Yang, Tiangang Wang, Xi Liu, Xiaobo Zhou, Liyu Huang
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Abstract

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.

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CAFuncAPA:人类癌症APA事件的系统功能注释的知识库。
选择性多腺苷酸化(APA)是一个广泛的转录后调控过程。APA产生具有不同3’UTR长度的不同mRNA亚型,影响mRNA表达、miRNA结合调节和选择性剪接事件。先前的研究已经通过不同方面证明了APA在肿瘤发生和癌症进展中的重要作用。因此,对不同APA事件的全面功能景观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,我们建造了CAFuncAPA(https://relab.xidian.edu.cn/CAFuncAPA/)以系统地注释15478个APA事件在人类泛癌中的功能。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、RNA结合蛋白(RBPs)和选择性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poly(A)位点和RBPs的影响,以及甲基化表型对APA事件影响。这些发现表明,CAFuncAPA可以成为更好地了解APA调节因子和癌症生物学中潜在功能的有用资源。
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