DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression.
DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression.
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DOI：
10.7150/jca.69216
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发表时间：
2022
影响因子：
3.9
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Lu P;Yu Z;Wang K;Zhai Y;Chen B;Liu M;Xu P;Li F;Zhao Q
DEAD-box RNA helicase 21（DDX 21）是一种具有ATP依赖性双链RNA解旋活性的核仁蛋白，在rRNA加工和核糖体生物合成中起重要作用。然而，其在结直肠癌（CRC）进展中的作用仍不清楚。在这项研究中，我们发现敲低DDX 21显著抑制CRC细胞增殖，并将细胞周期阻滞在G2/M期。基因图谱分析和ChIP检测显示，DDX 21通过与基因启动子结合激活CDK 1基因表达。此外，我们发现DDX 21直接募集WDR 5以增强CDK 1启动子上的Lys 4（H3 K4 me 3）上的组蛋白H3的三甲基化。重要的是，CRC患者中DDX 21的表达升高与CDK 1的表达呈正相关，这些CRC患者的总生存期较短。这些发现揭示了DDX 21在CRC细胞增殖的转录和表观遗传控制中的关键新作用。综上所述，本研究揭示了DDX 21与WDR 5相互作用，通过激活CDK 1表达促进结直肠癌细胞增殖，表明靶向DDX 21可能是CRC治疗的替代新策略。
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.