The landscape and clinical relevance of intronic polyadenylation in human cancers

Xiaomeng Cheng; Guanghui Jiang; Xiaolan Zhou; Jing Wang; Zhaozhao Zhao; Jiayu Zhang; Ting Ni

doi:10.1016/j.jgg.2024.04.014

The landscape and clinical relevance of intronic polyadenylation in human cancers

J Genet Genomics. 2024 May 11:S1673-8527(24)00099-7. doi: 10.1016/j.jgg.2024.04.014. Online ahead of print.

Authors

Xiaomeng Cheng¹, Guanghui Jiang¹, Xiaolan Zhou¹, Jing Wang¹, Zhaozhao Zhao², Jiayu Zhang¹, Ting Ni³

Affiliations

¹ State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Center for Evolutionary Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China.
² State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Center for Evolutionary Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China; MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, China.
³ State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Center for Evolutionary Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China; State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia 010070, China. Electronic address: tingni@fudan.edu.cn.

PMID: 38740258
DOI: 10.1016/j.jgg.2024.04.014

Abstract

Intronic polyadenylation (IPA) is an RNA 3' end processing event which has been reported to play important roles in cancer development. However, the comprehensive landscape of IPA events across various cancer types is lacking. Here, we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas (TCGA) project. We totally identify 21,835 IPA events, almost half of which are ubiquitously expressed. We identify 2,761 unique dynamically changed IPA events across cancer types. Furthermore, we observe 8,855 non-redundant clinically relevant IPA events, which could potentially be used as prognostic indicators. Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response. Finally, we develop a user-friendly data portal, IPACancer Atlas (http://www.tingni-lab.com/Pancan_IPA/), to search and explore IPAs in cancer.

Keywords: Cancer; Database; Drug sensitivity; Intronic polyadenylation; Single nucleotide variant.