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Published on: May 17, 2013
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.
Abstract:
DEAD-box RNA helicase 21 (DDX21), is a nucleolar protein harboring ATP-dependent double-stranded RNA unwinding activities, essential in rRNA processing and ribosome biogenesis. However, its role in colorectal cancer (CRC) progression remains unclear. In this study, we show that knockdown of DDX21 significantly inhibited CRC cell proliferation and blocked cell cycle at the G2/M phase. Gene profile analysis and ChIP assays revealed that DDX21 activated CDK1 gene expression through binding to the gene promoter. In addition, we found that DDX21 directly recruited WDR5 to enhance trimethylation of histone H3 on Lys 4 (H3K4me3) on the CDK1 promoter. Importantly, elevated expression of DDX21 in CRC patients was positively correlated with expression of CDK1, and these CRC patients had shorter overall survival. These findings reveal a critical novel role of DDX21 in transcriptional and epigenetic control of CRC cell proliferation. Taken together, this study uncovers that DDX21 interacted with WDR5 to promote colorectal cancer cell proliferation by activating CDK1 expression, suggesting that targeting DDX21 may be an alternative new strategy for CRC treatment.
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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