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.

Ddx56 maintains proliferation of mouse embryonic stem cells via ribosome assembly and interaction with the Oct4/Sox2 complex

“…It was not clear whether Bmi1, Egfr, and Kdr were Sox2 target genes. In addition, knockdown of Ddx56 suspended cell cycle progression from G2M to G1 phase in colorectal cancer cell line [42]. These data were consistent in Ddx56 ΔC-ter expressing mESCs in our study.…”

The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer

“…Members of the DEAD box (DDX) RNA helicase family are characterized by the presence of a conserved DEAD motif (Asp-Glu-Ala-Asp) and required for virtually all cellular RNA metabolic processes, including transcription, splicing, ribosome biogenesis, nuclear export, translation, and degradation 8,9 . Hence, the deregulation of DDXs may result in the disruption of RNA processing and may exert detrimental effects on the expression of certain key genes, such as oncogenes and tumor suppressors [10][11][12] . Therefore, cancer cells may rely on DDXs to attain increased expression of oncogenes and decreased production of tumor suppressors to promote cancer survival.…”

Determining the Clinical Value and Critical Pathway of GTPBP4 in Lung Adenocarcinoma Using a Bioinformatics Strategy: A Study Based on Datasets from The Cancer Genome Atlas

“…BOP1 (Block of Proliferation 1) is responsible for modulating pre-rRNA processing of 28S and 5.8S rRNAs [ 31 , 32 ]. Additionally, DEAD-box RNA helicase 56 (DDX56) is involved in the assembly of the 60S large ribosomal subunit and has been associated with lymphatic invasion and distant metastasis in CRC [ 33 ]. Pescadillo ribosomal biogenesis factor 1 (PES1), which has been reported as an independent poor prognostic factor in pancreatic cancer patients [ 34 ], is essential for 60S ribosomal subunit maturation and pre-rRNA processing [ 35 ].…”