Open AccessOncogenic splicing abnormalities induced by DEAD ‐Box Helicase 56 amplification in colorectal cancer
Author(s) -
Kouyama Yuta,
Masuda Takaaki,
Fujii Atsushi,
Ogawa Yushi,
Sato Kuniaki,
Tobo Taro,
Wakiyama Hiroaki,
Yoshikawa Yukihiro,
Noda Miwa,
Tsuruda Yusuke,
Kuroda Yousuke,
Eguchi Hidetoshi,
Ishida Fumio,
Kudo Shinei,
Mimori Koshi
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14163
Subject(s) - gene knockdown , cancer research , biology , rna splicing , oncogene , colorectal cancer , cancer , alternative splicing , cell cycle , gene , rna , messenger rna , genetics
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 DDX 56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas ( TCGA ) dataset of colorectal cancer ( CRC ). DDX 56 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 DDX 56 were explored by gene set enrichment analysis ( GSEA ), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX 56 ‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX 56 on mRNA splicing. We found that DDX 56 expression was positively correlated with the amplification of DDX 56 and was upregulated in CRC cells. High DDX 56 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 DDX 56 promoted proliferation ability through regulating the cell cycle. DDX 56 knockdown reduced intron retention and tumor suppressor WEE 1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX 56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE 1.