In:
Cancer Science, Wiley, Vol. 110, No. 10 ( 2019-10), p. 3132-3144
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 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.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6