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

Yuta Kouyama1,2, Takaaki Masuda1, Atsushi Fujii1

  • 1Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan.

Cancer Science
|August 8, 2019
PubMed

Insights

DEAD-Box Helicase 56 (DDX56) is a novel oncogene in colorectal cancer (CRC). Upregulated DDX56 promotes CRC cell proliferation and is a poor prognostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alternative splicing, regulated by DEAD-Box Helicase (DDX) proteins, is crucial in cancer development.
  • The specific role of the DDX family, particularly DDX56, in colorectal cancer (CRC) remains incompletely understood.

Purpose of the Study:

  • To investigate DDX56 as a potential oncogene and prognostic biomarker in colorectal cancer.
  • To elucidate the molecular mechanisms by which DDX56 influences CRC progression.

Main Methods:

  • Bioinformatic analysis of The Cancer Genome Atlas (TCGA) dataset for colorectal cancer.
  • Quantitative real-time PCR (RT-qPCR) and immunohistochemical staining to assess DDX56 expression in patient samples.
  • In vitro and in vivo assays, gene set enrichment analysis (GSEA), and RNA sequencing to study DDX56 function and its effect on mRNA splicing.

Main Results:

  • DDX56 was identified as a candidate oncogene on chromosome 7p and found to be upregulated in CRC cells, correlating with gene amplification.
  • High DDX56 expression was significantly associated with lymphatic invasion, distant metastasis, and served as an independent poor prognostic factor in CRC patients.
  • DDX56 promoted cell proliferation by regulating the cell cycle and was found to influence alternative splicing, specifically reducing WEE1 expression.

Conclusions:

  • DDX56 is a novel oncogene and a valuable prognostic biomarker for colorectal cancer.
  • DDX56 promotes CRC progression through regulating the cell cycle and alternative splicing of the WEE1 gene, a critical component of the G2-M DNA damage checkpoint.

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