TY - JOUR
T1 - A functional network of gastric-cancer-associated splicing events controlled by dysregulated splicing factors
AU - Cheng, Shanshan
AU - Ray, Debleena
AU - Lee, Raymond Teck Ho
AU - Naripogu, Kishore Babu
AU - Yusoff, Permeen Akhtar Bt Mohamed
AU - Goh, Pamela Bee Leng
AU - Liu, Yujing
AU - Suzuki, Yuka
AU - Das, Kakoli
AU - Chan, Hsiang Sui
AU - Wong, Wai Keong
AU - Chan, Weng Hoong
AU - Chow, Pierce Kah Hoe
AU - Ong, Hock Soo
AU - Raj, Prema
AU - Soo, Khee Chee
AU - Tan, Patrick
AU - Epstein, David M.
AU - Rozen, Steven G.
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor–normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and stringent filtering, and also identified 8 differentially expressed splicing factors (SFs). The TA ASEs occurred in genes primarily involved in cytoskeletal organization. We constructed a correlative network between TA ASE splicing ratios and SF expression, replicated it in independent gastric cancer data from The Cancer Genome Atlas and experimentally validated it by knockdown of the nodal SFs (PTBP1, ESRP2 and MBNL1). Each SF knockdown drove splicing alterations in several corresponding TA ASEs and led to alterations in cellular migration consistent with the role of TA ASEs in cytoskeletal organization. We have therefore established a robust network of dysregulated splicing associated with tumor invasion in gastric cancer. Our work is a resource for identifying oncogenic splice forms, SFs and splicing-generated tumor antigens as biomarkers and therapeutic targets.
AB - Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor–normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and stringent filtering, and also identified 8 differentially expressed splicing factors (SFs). The TA ASEs occurred in genes primarily involved in cytoskeletal organization. We constructed a correlative network between TA ASE splicing ratios and SF expression, replicated it in independent gastric cancer data from The Cancer Genome Atlas and experimentally validated it by knockdown of the nodal SFs (PTBP1, ESRP2 and MBNL1). Each SF knockdown drove splicing alterations in several corresponding TA ASEs and led to alterations in cellular migration consistent with the role of TA ASEs in cytoskeletal organization. We have therefore established a robust network of dysregulated splicing associated with tumor invasion in gastric cancer. Our work is a resource for identifying oncogenic splice forms, SFs and splicing-generated tumor antigens as biomarkers and therapeutic targets.
UR - https://www.scopus.com/pages/publications/85088424665
U2 - 10.1093/nargab/lqaa013
DO - 10.1093/nargab/lqaa013
M3 - 文章
AN - SCOPUS:85088424665
SN - 2631-9268
VL - 2
JO - NAR Genomics and Bioinformatics
JF - NAR Genomics and Bioinformatics
IS - 2
M1 - lqaa013
ER -
