J Cancer 2022; 13(5):1530-1539. doi:10.7150/jca.69216 This issue

Research Paper

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

Peifen Lu1, Zenong Yu1, Kangning Wang1, Yongping Zhai2, Bing Chen1, Ming Liu1, Peipei Xu1✉, Feng Li2✉, Quan Zhao1✉

1. The 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.
2. Department of Hematology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

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Lu P, Yu Z, Wang K, Zhai Y, Chen B, Liu M, Xu P, Li F, Zhao Q. DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression. J Cancer 2022; 13(5):1530-1539. doi:10.7150/jca.69216. Available from https://www.jcancer.org/v13p1530.htm

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Graphic 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.

Keywords: DDX21, WDR5, CDK1, H3K4me3, Colorectal Cancer