Dhx15, also known as DEAH-box helicase 15, is an ATP-dependent RNA helicase mainly involved in RNA metabolism, such as RNA splicing and ribosome maturation [1,4,6]. It is associated with multiple biological pathways including the Wnt signaling pathway, unfolded protein response pathway, and is involved in processes like autophagy regulation [1,4,7]. Dhx15 is of great biological importance in various tissues' development, immunity, and disease-related processes. Genetic models like zebrafish and mice are valuable for studying Dhx15.

In zebrafish, dhx15 knockout leads to profound intestinal defects, with decreased intestinal cell proliferation, increased apoptosis, and down-regulation of the Wnt signaling pathway, indicating its role in intestinal development [1]. In T-cell acute lymphoblastic leukemia (T-ALL) murine models, DHX15 is essential for tumor cell survival and leukemogenesis. Its depletion hinders T-cell progenitor proliferation, perturbs RNA splicing, and suppresses glutamine import and mTORC1 activity [2]. In Villin-Cre/KrasG12D+/- mice, knockout of Dhx15 attenuates the colorectal cancer (CRC) phenotype as Fusobacterium nucleatum promotes CRC progression by binding to DHX15 [3]. In IEC-specific Dhx15-knockout mice, DHX15 is required to control intestinal inflammation induced by enteric RNA viruses, as it is essential for the production of type I interferon, type III interferon, and inflammasome-derived cytokine IL-18 by intestinal epithelial cells [5]. In zebrafish, dhx15 -/- leads to perturbed hematopoietic stem/progenitor cells through the unfolded protein response pathway [7]. In mice, Dhx15 gene deficiency impairs liver organogenesis in embryos and liver regeneration after partial hepatectomy, and its silencing hinders primary tumor growth in a hepatocellular carcinoma model [8].

In conclusion, Dhx15 plays essential roles in multiple biological processes including tissue development, hematopoiesis, and immunity. Studies using gene knockout models in zebrafish and mice have revealed its significance in diseases such as leukemia, CRC, and liver cancer, as well as in controlling intestinal inflammation. These findings contribute to understanding disease mechanisms and may offer potential therapeutic targets.