Genome-wide profiling of polyadenylation sites reveals a link between selective polyadenylation and cancer metastasis

Human Molecular Genetics
Deng-Pan LaiXiaodong Zhao

Abstract

Alternative polyadenylation (APA) is an important post-transcriptional modification implicated in many diseases, including cancer. Although extensively characterized, the functional consequence of APA modulation on tumorigenesis remains elusive. Here, we developed a deep sequencing-based approach that specifically profiles 3' termini of polyadenylated RNAs (herein termed 3T-seq) and analyzed APA events in two gastric cancer cell lines and one non-transformed counterpart. Overall, we identified >28 000 poly(A) sites, 70% of which are potentially novel. Further, we observed widespread APA-mediated 3' UTR shortening of 513 genes (false discovery rate < 0.05) across gastric cancer genome. We characterized one of these genes, NET1, in detail and found that the shortening of NET1 3' UTR significantly enhances transcriptional activity. Moreover, the NET1 isoform with short 3' UTR promotes cellular migration and invasion in vitro. Collectively, our work provides an effective approach for genome-wide APA site profiling and reveals a link between APA modulation and gastric cancer metastasis.

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Citations

Nov 1, 2016·Nature Reviews. Genetics·Cameron P BrackenGregory J Goodall
Oct 13, 2017·PLoS Genetics·Allison L RichardsFrancesca Luca
Dec 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yao KouJing Tian
Mar 24, 2017·Nucleic Acids Research·Shaked AfikSebastian Kadener
Feb 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yi ZhangPengyuan Liu
Mar 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Sheng TanXiaodong Zhao
Aug 4, 2020·Asian Journal of Urology·Ieva EringyteClaire E Fletcher
Apr 13, 2021·Wiley Interdisciplinary Reviews. RNA·Isabel Pereira-Castro, Alexandra Moreira
Sep 29, 2021·Wiley Interdisciplinary Reviews. RNA·Neeraja K MohananRakesh S Laishram

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