title: Genome-wide profiling of polyadenylation sites reveals a link between selective polyadenylation and cancer metastasis.
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.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital.
authors.forename: Deng-Pan
authors.initials: DP
authors.lastname: Lai
authors.affiliation: Laboratory of Molecular Tumor Pathology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tan
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital.
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Kang
authors.affiliation: Department of Automation and.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Denmark and.
authors.forename: Hong-Sain
authors.initials: HS
authors.lastname: Ooi
authors.affiliation: Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Shen
authors.affiliation: Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Laboratory of Molecular Tumor Pathology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China, Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, China.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shao
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Bio-ID Center, School of Biomedical Engineering, Ruijin Hospital, xiaodongzhao@sjtu.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D026723:Polyadenylation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger