The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer.

Chengcheng He, Aimin Li, Qiuhua Lai, Jian Ding, Qun Yan, Side Liu, Qingyuan Li

Cell death & disease 2021 Jan 12

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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.

Citation

Chengcheng He, Aimin Li, Qiuhua Lai, Jian Ding, Qun Yan, Side Liu, Qingyuan Li. The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer. Cell death & disease. 2021 Jan 12;12(1):74