Ddx17, a member of the DEAD-box RNA helicase family, is a nuclear and cytoplasmic shuttle protein [3]. It participates in multiple RNA metabolism processes such as alternative splicing of mRNA, biogenesis of microRNAs and ribosomes, mRNA degradation, interaction with long non-coding RNAs, and coregulation of transcriptional activity [3]. It is involved in various biological processes and is associated with many diseases including cancer and heart failure. Genetic models, like knockout mouse models, are valuable for studying its functions.

In hepatocellular carcinoma (HCC), Ddx17 knockout inhibited extracellular matrix degradation and HCC cell invasion, and reduced lung metastasis in a Ddx17HKO mouse model. High Ddx17 levels induced an intron retention in PXN-AS1, generating a transcript (PXN-AS1-IR3) that promoted HCC metastasis via the MYC signaling pathway [1]. In heart failure, cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO) showed autophagic flux blockage, cardiomyocyte apoptosis, and progressive cardiac dysfunction. Ddx17 protected cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway [2]. In colorectal cancer, Ddx17-deficient cells had reduced migration and invasion abilities. Ddx17 promoted metastasis and epithelial-mesenchymal transition via the miR-149-3p/CYBRD1 pathway [4]. In lung adenocarcinoma, Ddx17 promoted cell proliferation, migration, and invasion in vitro, and growth and metastasis in tumor xenograft models in vivo [5].

In summary, Ddx17 is multifunctional, playing important roles in processes like tumor metastasis and cardiac function. Gene knockout models, such as in HCC, heart failure, colorectal cancer, and lung adenocarcinoma studies, have significantly enhanced our understanding of Ddx17's functions in these disease conditions, revealing its potential as a prognostic marker and therapeutic target.

References:

1. Zhou, Hong-Zhong, Li, Fan, Cheng, Sheng-Tao, Huang, Ai-Long, Chen, Juan. 2021. DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis. In Hepatology (Baltimore, Md.), 75, 847-865. doi:10.1002/hep.32195. https://pubmed.ncbi.nlm.nih.gov/34626132/

2. Yan, Mingjing, Gao, Junpeng, Lan, Ming, Li, Jian, Shen, Tao. 2024. DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure. In Signal transduction and targeted therapy, 9, 127. doi:10.1038/s41392-024-01831-2. https://pubmed.ncbi.nlm.nih.gov/38782919/

3. Xu, Kun, Sun, Shenghui, Yan, Mingjing, Li, Jian, Shen, Tao. 2022. DDX5 and DDX17-multifaceted proteins in the regulation of tumorigenesis and tumor progression. In Frontiers in oncology, 12, 943032. doi:10.3389/fonc.2022.943032. https://pubmed.ncbi.nlm.nih.gov/35992805/

4. Zhao, Gang, Wang, Qijing, Zhang, Yue, Mo, Chunfen, Lin, Ping. 2023. DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer. In Cell death & disease, 14, 1. doi:10.1038/s41419-022-05508-y. https://pubmed.ncbi.nlm.nih.gov/36593242/

5. Liu, Xiaohui, Li, Lu, Geng, Chengjie, He, Qing-Yu, Liu, Langxia. 2022. DDX17 promotes the growth and metastasis of lung adenocarcinoma. In Cell death discovery, 8, 425. doi:10.1038/s41420-022-01215-x. https://pubmed.ncbi.nlm.nih.gov/36273228/