Ddx60, an interferon-inducible cytoplasmic helicase, is involved in multiple biological processes. It plays a role in antiviral innate immune responses, such as being a sentinel for RIG-I activation and viral RNA degradation, and is part of pathways like the IFN-I-induced antiviral activities and RIG-I signaling [6,8]. It is also associated with various diseases including cancer and autoimmune diseases, highlighting its overall biological importance. Genetic models can be valuable for studying its functions in vivo.

In colorectal cancer, oncogenic KRAS down-regulates Ddx60, accelerating dsRNA degradation and impairing the IFN response, and overexpressing Ddx60 can reactivate IFN signaling and increase sensitivity to immune checkpoint inhibition therapy [1]. In exercise hypertrophic preconditioning in mice, silencing of circ-Ddx60 (derived from Ddx60) attenuated the antihypertrophic effect and worsened heart failure after transverse aortic constriction, suggesting its role in cardiac protection [2]. In head and neck squamous cell carcinoma, Ddx60 promotes cell migration, invasion, and epithelial-to-mesenchymal transition via the NF-κB/IFI27 axis [3]. In glioma, it is upregulated, associated with immune-related functions and could be a potential immunotherapy biomarker [4]. In pancreatic cancer, Ddx60 is upregulated, promotes cell proliferation, migration, and invasion, and is related to poor prognosis and immune resistance [5]. In systemic lupus erythematosus, Ddx60 is highly expressed in patients with high disease activity and might be a potential biomarker [7].

In conclusion, Ddx60 is crucial for antiviral innate immune responses and is significantly involved in various disease conditions including different cancers and an autoimmune disease. Studies using knockout or knockdown models in different contexts have revealed its functions in disease-related biological processes, providing insights into potential therapeutic targets for these diseases.

References:

1. Zhou, Yi, Zhang, Yaxin, Li, Mingzhou, Huang, Huilin, Liao, Wenting. 2024. Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry. In Science immunology, 9, eado8758. doi:10.1126/sciimmunol.ado8758. https://pubmed.ncbi.nlm.nih.gov/39365875/

2. Zhu, Yingqi, Zheng, Cankun, Zhang, Rui, Lin, Hairuo, Liao, Yulin. 2022. Circ-Ddx60 contributes to the antihypertrophic memory of exercise hypertrophic preconditioning. In Journal of advanced research, 46, 113-121. doi:10.1016/j.jare.2022.06.005. https://pubmed.ncbi.nlm.nih.gov/35718079/

3. Han, Yumei, Gao, Jinbo, Liu, Lei. . DDX60 Promotes Migration and Invasion of Head and Neck Squamous Cell Carcinoma Cell through the NF-κB/IFI27 Signaling Pathway. In Frontiers in bioscience (Landmark edition), 29, 14. doi:10.31083/j.fbl2901014. https://pubmed.ncbi.nlm.nih.gov/38287816/

4. Zhang, Jingwen, Fu, Minjie, Zhang, Mengli, Hua, Wei, Mao, Ying. 2021. DDX60 Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker. In Frontiers in oncology, 11, 665360. doi:10.3389/fonc.2021.665360. https://pubmed.ncbi.nlm.nih.gov/34178649/

5. Lai, Tiantian, Su, Xiaowen, Chen, Enhong, Mao, Yong, Hu, Hao. 2023. The DEAD-box RNA helicase, DDX60, Suppresses immunotherapy and promotes malignant progression of pancreatic cancer. In Biochemistry and biophysics reports, 34, 101488. doi:10.1016/j.bbrep.2023.101488. https://pubmed.ncbi.nlm.nih.gov/37274827/

6. Schoggins, John W, Wilson, Sam J, Panis, Maryline, Bieniasz, Paul, Rice, Charles M. 2011. A diverse range of gene products are effectors of the type I interferon antiviral response. In Nature, 472, 481-5. doi:10.1038/nature09907. https://pubmed.ncbi.nlm.nih.gov/21478870/

7. Chen, Wu, Li, Zhi-Yu, Huang, Lin, Wen, Cheng-Ping, Wang, Qiao. 2023. Integrative Bioinformatics Analysis Identifies DDX60 as a Potential Biomarker for Systemic Lupus Erythematosus. In Disease markers, 2023, 8564650. doi:10.1155/2023/8564650. https://pubmed.ncbi.nlm.nih.gov/36655136/

8. Oshiumi, Hiroyuki, Miyashita, Moeko, Okamoto, Masaaki, Matsumoto, Misako, Seya, Tsukasa. 2015. DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation. In Cell reports, 11, 1193-207. doi:10.1016/j.celrep.2015.04.047. https://pubmed.ncbi.nlm.nih.gov/25981042/