DDX39B is a member of the DEAD box (DDX) RNA helicase family required for nearly all cellular RNA metabolic processes. The exact role and potential molecular mechanism of DDX39B in the progression of human colorectal cancer (CRC) remain to be investigated. In the present study, we demonstrate that DDX39B expression is higher in CRC tissues than in adjacent normal tissues. Gain- and loss-of-function assays revealed that DDX39B facilitates CRC metastasis in vivo and in vitro. Mechanistically, RNA-sequencing (RNA-seq) and RNA-binding protein immunoprecipitation-sequencing (RIP-seq) showed that DDX39B binds directly to the FUT3 pre-mRNA and upregulates FUT3 expression. Splicing experiments in vitro using a Minigene assay confirmed that DDX39B promotes FUT3 pre-mRNA splicing. A nuclear and cytoplasmic RNA separation assay indicates that DDX39B enhances the mRNA export of FUT3. Upregulation of FUT3 accelerates the fucosylation of TGFβR-I, which activates the TGFβ signaling pathway and eventually drives the epithelial–mesenchymal transition (EMT) program and contributes to CRC progression. These findings not only provide new insight into the role of DDX39B in mRNA splicing and export as well as in tumorigenesis, but also shed light on the effects of aberrant fucosylation on CRC progression.

DDX39B 是几乎所有细胞 RNA 代谢过程所需的死盒 (DDX) RNA 解旋酶家族的成员。DDX39B 在人类结直肠癌 (CRC) 进展中的确切作用和潜在分子机制仍有待研究。在本研究中，我们证明 DDX39B 在 CRC 组织中的表达高于在相邻正常组织中的表达。功能获得和功能丧失分析表明，DDX39B 在体内和体外促进 CRC 转移。从机制上讲，RNA 测序 (RNA-seq) 和 RNA 结合蛋白免疫沉淀测序 (RIP-seq) 表明 DDX39B 直接与 FUT3 前 mRNA 结合并上调 FUT3 表达。使用 Minigene 测定的体外剪接实验证实 DDX39B 促进 FUT3 前体 mRNA 剪接。核和细胞质 RNA 分离试验表明 DDX39B 增强了 FUT3 的 mRNA 输出。FUT3 的上调会加速 TGFβR-I 的岩藻糖基化，从而激活 TGFβ 信号通路并最终驱动上皮间质转化 (EMT) 程序并促进 CRC 进展。这些发现不仅为 DDX39B 在 mRNA 剪接和输出以及肿瘤发生中的作用提供了新的见解，而且还阐明了异常岩藻糖基化对 CRC 进展的影响。