Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer

Yuta Kouyama, Takaaki Masuda, Atsushi Fujii, Yushi Ogawa, Kuniaki Sato, Taro Tobo, Hiroaki Wakiyama, Yukihiro Yoshikawa, Miwa Noda, Yusuke Tsuruda, Yousuke Kuroda, Hidetoshi Eguchi, Fumio Ishida, Shin ei Kudo, Koshi Mimori

研究成果: Contribution to journalArticle査読

21 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)3132-3144
ページ数13
ジャーナルCancer Science
110
10
DOI
出版ステータス出版済み - 10 1 2019
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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