DDX18, also known as DEAD-box RNA helicase 18, is a crucial regulator of RNA metabolism. It participates in various cellular processes, including cell-cycle control, and is involved in pathways related to R-loop homeostasis, chromatin remodeling, and nucleolus phase separation. It plays a significant role in maintaining genomic stability, pluripotency of stem cells, and is associated with multiple disease-related processes [1,3,4,5].

In zebrafish, Ddx18 is essential for cell-cycle progression in hematopoietic cells. Homozygous Ddx18 mutant embryos show a profound loss of myeloid and erythroid cells, along with apoptosis and G1 cell-cycle arrest [7]. In human cells, Ddx18 depletion leads to aberrant R-loop accumulation, DNA-replication defects, and genome instability. RNase H1 overexpression can rescue these DNA-repair defects caused by Ddx18 depletion [1]. In pancreatic cancer, DDX18 drives tumor immune escape by up-regulating STAT1 expression [2]. In lung adenocarcinoma, DDX18 promotes tumorigenesis by up-regulating CDK4 and facilitating cell-cycle progression [4]. In colorectal cancer, DDX18 affects chemotherapy sensitivity by regulating genomic stability [5]. In gastric cancer, DDX18 promotes cancer by influencing the maturation of microRNA-21 [6]. In human head and neck squamous cell carcinoma, DNA 6mA demethylase ALKBH1 regulates DDX18 expression to promote cell proliferation [8]. In porcine reproductive and respiratory syndrome virus infection, host DDX18 unwinds a G-quadruplex structure in the viral genome to promote viral replication [9]. In pigs, DDX18 is one of the hub genes that helps in vivo-matured oocytes resist post-ovulatory aging [10].

In conclusion, DDX18 is a multi-functional gene involved in RNA metabolism, cell-cycle regulation, and maintaining genomic stability. Through gene-knockout and other in vivo models in zebrafish and human cells, its role in various diseases such as cancer, viral infection, and oocyte aging has been revealed. Understanding DDX18 provides insights into disease mechanisms and potential therapeutic targets.