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

Deng Pan Lai; Sheng Tan; Ya Ni Kang; Jun Wu; Hong Sain Ooi; Jian Chen; Ting Ting Shen; Ying Qi; Xiaoli Zhang; Yan Guo; Tao Zhu; Bingya Liu; Zhifeng Shao; Xiaodong Zhao

doi:10.1093/hmg/ddv089

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

Deng Pan Lai
, Sheng Tan
, Ya Ni Kang
, Jun Wu
, Hong Sain Ooi
, Jian Chen
, Ting Ting Shen
, Ying Qi
, Xiaoli Zhang
, Yan Guo
, Tao Zhu
, Bingya Liu
, Zhifeng Shao
, Xiaodong Zhao^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

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.

Original language	English
Article number	ddv089
Pages (from-to)	3410-3417
Number of pages	8
Journal	Human Molecular Genetics
Volume	24
Issue number	12
DOIs	https://doi.org/10.1093/hmg/ddv089
State	Published - 18 Jan 2015
Externally published	Yes

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@article{474de1520d124d59b7f86886974a7142,

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.",

author = "Lai, \{Deng Pan\} and Sheng Tan and Kang, \{Ya Ni\} and Jun Wu and Ooi, \{Hong Sain\} and Jian Chen and Shen, \{Ting Ting\} and Ying Qi and Xiaoli Zhang and Yan Guo and Tao Zhu and Bingya Liu and Zhifeng Shao and Xiaodong Zhao",

year = "2015",

month = jan,

day = "18",

doi = "10.1093/hmg/ddv089",

language = "英语",

volume = "24",

pages = "3410--3417",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "12",

}

TY - JOUR

T1 - Genome-wide profiling of polyadenylation sites reveals a link between selective polyadenylation and cancer metastasis

AU - Lai, Deng Pan

AU - Tan, Sheng

AU - Kang, Ya Ni

AU - Wu, Jun

AU - Ooi, Hong Sain

AU - Chen, Jian

AU - Shen, Ting Ting

AU - Qi, Ying

AU - Zhang, Xiaoli

AU - Guo, Yan

AU - Zhu, Tao

AU - Liu, Bingya

AU - Shao, Zhifeng

AU - Zhao, Xiaodong

PY - 2015/1/18

Y1 - 2015/1/18

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84930448501

U2 - 10.1093/hmg/ddv089

DO - 10.1093/hmg/ddv089

M3 - 文章

C2 - 25759468

AN - SCOPUS:84930448501

SN - 0964-6906

VL - 24

SP - 3410

EP - 3417

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 12

M1 - ddv089

ER -

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

Abstract

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