@article{fbaf735ab41549cb94e23215d32f86b6,
title = "Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer",
abstract = "Alternative splicing, regulated by DEAD-Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT-qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56-knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2-M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1.",
author = "Yuta Kouyama and Takaaki Masuda and Atsushi Fujii and Yushi Ogawa and Kuniaki Sato and Taro Tobo and hiroaki wakiyama and Yukihiro Yoshikawa and Miwa Noda and Yusuke Tsuruda and Yohsuke Kuroda and Hidetoshi Eguchi and Fumio Ishida and Kudo, {Shin ei} and Koshi Mimori",
note = "Funding Information: This research used the super‐computing resource provided by the Human Genome Center, The Institute of Medical Science, The University of Tokyo ( http://sc.hgc.jp/shirokane.html ). We thank K. Oda, M. Kasagi, M. Sakuma, N. Mishima and T. Kawano for their technical assistance. This work was supported in part by the following grants and foundations: Japan Society for the Promotion of Science (JSPS) Grant‐in‐Aid for Science Research (grant numbers JP16K07177, JP16K10543, JP16K19197, JP17K16454, JP17K16521, JP17K10593 and JP17K19608); OITA Cancer Research Foundation; Daiwa Securities Health Foundation; Grant‐in‐Aid for Scientific Research on Innovative Areas (15H0912); Priority Issue on Post‐K computer (hp170227, hp160219); JSPS KAKENHI (15H05707); Eli Lilly Japan K.K. grant; Japanese Foundation for Multidisciplinary Treatment of Cancer. Funding Information: This research used the super-computing resource provided by the Human Genome Center, The Institute of Medical Science, The University of Tokyo (http://sc.hgc.jp/shirokane.html). We thank K. Oda, M. Kasagi, M. Sakuma, N. Mishima and T. Kawano for their technical assistance. This work was supported in part by the following grants and foundations: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research (grant numbers JP16K07177, JP16K10543, JP16K19197, JP17K16454, JP17K16521, JP17K10593 and JP17K19608); OITA Cancer Research Foundation; Daiwa Securities Health Foundation; Grant-in-Aid for Scientific Research on Innovative Areas (15H0912); Priority Issue on Post-K computer (hp170227, hp160219); JSPS KAKENHI (15H05707); Eli Lilly Japan K.K. grant; Japanese Foundation for Multidisciplinary Treatment of Cancer. Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2019",
month = oct,
day = "1",
doi = "10.1111/cas.14163",
language = "English",
volume = "110",
pages = "3132--3144",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "10",
}