DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression

Peifen Lu1, Zenong Yu1, Kangning Wang1

  • 1The State Key Laboratory of Pharmaceutical Biotechnology, Department of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, China-Australia Institute of Translational Medicine, School of Life Sciences, Nanjing University, Nanjing, China.

Journal of Cancer
|April 4, 2022
PubMed

Insights

DEAD-box RNA helicase 21 (DDX21) promotes colorectal cancer (CRC) cell proliferation by activating CDK1. Targeting DDX21 may offer a new therapeutic strategy for CRC patients with elevated DDX21 expression.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • DEAD-box RNA helicase 21 (DDX21) is crucial for rRNA processing and ribosome biogenesis.
  • The role of DDX21 in colorectal cancer (CRC) progression is not well understood.

Purpose of the Study:

  • To investigate the role of DDX21 in colorectal cancer (CRC) cell proliferation.
  • To elucidate the molecular mechanisms by which DDX21 influences CRC progression.

Main Methods:

  • Knockdown of DDX21 in CRC cells.
  • Gene expression profiling and Chromatin Immunoprecipitation (ChIP) assays.
  • Analysis of DDX21 and CDK1 expression in CRC patient cohorts.

Main Results:

  • DDX21 knockdown inhibited CRC cell proliferation and caused G2/M cell cycle arrest.
  • DDX21 activates CDK1 gene expression by binding to its promoter.
  • DDX21 recruits WDR5 to enhance H3K4me3 methylation on the CDK1 promoter.
  • Elevated DDX21 expression correlates with CDK1 expression and reduced survival in CRC patients.

Conclusions:

  • DDX21 plays a critical role in the transcriptional and epigenetic control of CRC cell proliferation.
  • DDX21 promotes CRC cell proliferation by activating CDK1 expression via WDR5 recruitment and H3K4me3 modification.
  • Targeting DDX21 presents a potential new therapeutic strategy for colorectal cancer.

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