Ddx39b, also known as UAP56 or BAT1, is a member of the DEAD box (DDX) RNA helicase family, crucial for nearly all cellular RNA metabolic processes, such as mRNA binding, splicing, and export [2,3]. It has been implicated in pathways related to cell cycle regulation, glycolysis, and epithelial-mesenchymal transition, and is of great biological importance in cancer development and genomic stability [1-4]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can potentially provide in-depth insights into its functions.

In colorectal cancer (CRC), Ddx39B-deficient cells show reduced proliferation, migration, and invasion, indicating its oncogenic role. It directly interacts with and stabilizes PKM2, accelerating PKM2 nuclear translocation to activate oncogenes and glycolysis-related genes [1]. In addition, Ddx39B knockdown in CRC cells hinders cell cycle progression from G0/G1 to S phase by reducing the splicing and expression of CDK6/CCND1 [3]. In hepatocellular carcinoma, Ddx39B-silenced cells are more sensitive to sorafenib-induced ferroptosis as Ddx39B promotes the splicing and cytoplasmic export of GPX4 pre-mRNA [4]. Also, in pancreatic ductal adenocarcinoma, targeting Ddx39B with CCT018159 sensitizes cells to gemcitabine-induced apoptosis [5].

In conclusion, Ddx39b plays essential roles in multiple biological processes, especially in cancer-related pathways like cell proliferation, metastasis, and drug resistance. Findings from KO or knockdown models in various cancer types, such as colorectal, liver, and pancreatic cancers, have revealed its oncogenic functions, highlighting its potential as a therapeutic target in these diseases.

References:

1. Zhao, Gang, Yuan, Hang, Li, Qin, Li, Kai, Lin, Ping. 2022. DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2. In Signal transduction and targeted therapy, 7, 275. doi:10.1038/s41392-022-01096-7. https://pubmed.ncbi.nlm.nih.gov/35973989/

2. He, Chengcheng, Li, Aimin, Lai, Qiuhua, Liu, Side, Li, Qingyuan. 2021. The DDX39B/FUT3/TGFβR-I axis promotes tumor metastasis and EMT in colorectal cancer. In Cell death & disease, 12, 74. doi:10.1038/s41419-020-03360-6. https://pubmed.ncbi.nlm.nih.gov/33436563/

3. Zhang, Haonan, He, Chengcheng, Guo, Xuxue, Liu, Side, Li, Qingyuan. 2022. DDX39B contributes to the proliferation of colorectal cancer through direct binding to CDK6/CCND1. In Cell death discovery, 8, 30. doi:10.1038/s41420-022-00827-7. https://pubmed.ncbi.nlm.nih.gov/35046400/

4. Li, Qin, Yuan, Hang, Zhao, Gang, Lin, Ping, Li, Kai. 2024. DDX39B protects against sorafenib-induced ferroptosis by facilitating the splicing and cytoplasmic export of GPX4 pre-mRNA in hepatocellular carcinoma. In Biochemical pharmacology, 225, 116251. doi:10.1016/j.bcp.2024.116251. https://pubmed.ncbi.nlm.nih.gov/38701867/

5. Tu, Qiu, Liu, Xiuyun, Yao, Xiaoqing, Shi, Peng, Zhao, Bo. 2022. RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma. In Journal of experimental & clinical cancer research : CR, 41, 274. doi:10.1186/s13046-022-02490-3. https://pubmed.ncbi.nlm.nih.gov/36109793/