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.
References
Jan 1, 1995·Journal of Cell Science. Supplement·J D LewisI W Mattaj
Jan 1, 1996·Annual Review of Biochemistry·A Jacobson, S W Peltz
Apr 1, 1997·Current Opinion in Genetics & Development·M WickensR J Jackson
Jul 19, 2000·Genome Research·E BeaudoingD Gautheret
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Jan 14, 2005·Nucleic Acids Research·Bin TianCarol S Lutz
Dec 17, 2005·Genome Biology·Haibo ZhangBin Tian
Apr 5, 2007·Nature Protocols·Elizabeth Scotto-LavinoMichael A Frohman
Jun 21, 2008·Science·Rickard SandbergChristopher B Burge
Oct 2, 2008·British Journal of Cancer·D MurrayP Doran
Nov 4, 2008·Nature·Eric T WangChristopher B Burge
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Aug 26, 2009·Cell·Christine Mayr, David P Bartel
Mar 12, 2010·Nature·Joseph K PickrellJonathan K Pritchard
Apr 28, 2010·RNA·Oh Kyu Yoon, Rachel B Brem
Nov 4, 2010·Genome Research·Zhenhua Jeremy WuX Shirley Liu
Feb 24, 2011·RNA·Peter J ShepardYongsheng Shi
Apr 9, 2011·Genome Research·Yonggui FuAnlong Xu
Jun 11, 2011·FEBS Letters·Sheng TanTao Zhu
Sep 20, 2011·Molecular Cell·Dafne Campigli Di GiammartinoJames L Manley
Jun 9, 2012·FEBS Letters·Ming WangBingya Liu
Jul 4, 2012·Nucleic Acids Research·Yuefeng LinBino John
Jul 10, 2012·Nucleic Acids Research·Eleonora de KlerkPeter A C 't Hoen
Aug 10, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adam R MorrisReuven Agami
Oct 26, 2012·RNA·Yongsheng Shi
Oct 27, 2012·Journal of Molecular Cell Biology·Yu SunAnlong Xu
Jun 19, 2013·Nature Reviews. Genetics·Ran ElkonReuven Agami
Jul 23, 2013·Nature Protocols·Huaiyu MiPaul D Thomas
Oct 23, 2013·Genes & Development·Steve LianoglouChristine Mayr
Citations
May 14, 2016·Chinese Medical Journal·Xiang-Jun HeYu-Jun Zhang
Nov 1, 2016·Nature Reviews. Genetics·Cameron P BrackenGregory J Goodall
Nov 5, 2016·Scientific Reports·Hongyang WangBang Liu
Mar 30, 2017·Marine Drugs·Yani KangNianjun Xu
May 22, 2018·Oncogene·Sheng TanTao Zhu
Oct 13, 2017·PLoS Genetics·Allison L RichardsFrancesca Luca
Mar 17, 2018·Oncotarget·Yunwu WangJiazhi Liao
Dec 13, 2017·Nature Communications·Yuval MalkaMichael Berger
Dec 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yao KouJing Tian
Mar 24, 2017·Nucleic Acids Research·Shaked AfikSebastian Kadener
Mar 11, 2020·Frontiers in Genetics·Zhanrui MaoYani Kang
Oct 26, 2018·Journal of Biomedical Science·Ya-Fei XuLing-Long Tang
Jun 21, 2020·Biomolecules·Jamie NourseSven Danckwardt
Oct 22, 2020·Acta Biochimica Et Biophysica Sinica·Qiang ZhaoXiaodong Zhao
Jan 21, 2021·Cell Reports·Fabien MorettoFolkert J van Werven
Jan 16, 2021·Genome Biology·Minghao ChiaFolkert J van Werven
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
Jun 26, 2021·Frontiers in Oncology·Jian ZhangLin Zhu
Jun 24, 2019·Gene·Igor Araujo VieiraPatricia Ashton-Prolla
Sep 29, 2021·Wiley Interdisciplinary Reviews. RNA·Neeraja K MohananRakesh S Laishram
Oct 2, 2021·Frontiers in Genetics·Xinglong ShiJielin Sun