Ddx17-flox Mouse

Ddx17, a member of the DEAD-box RNA helicase family, is a nuclear and cytoplasmic shuttle protein with transcriptional cofactor activity [3]. It participates in almost all processes of RNA metabolism, such as mRNA alternative splicing, miRNA and ribosome biogenesis, mRNA degradation, interaction with lncRNAs, and co-regulation of transcriptional activity [3].

In hepatocellular carcinoma (HCC), Ddx17 knockout inhibited extracellular matrix degradation and the invasive ability of HCC cells. A Ddx17-deficient diethylnitrosamine-induced mouse model showed a significant reduction in lung metastasis. High Ddx17 levels induced intron 3 retention of PXN-AS1, producing a metastasis-promoting transcript that activated MYC transcription [1].

In heart failure, cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO) showed autophagic flux blockage, cardiomyocyte apoptosis, progressive cardiac dysfunction, and maladaptive remodeling, while restoration of DDX17 expression protected cardiac function. DDX17 binds to BCL6 and inhibits DRP1 expression, maintaining mitochondrial homeostasis [2].

In colorectal cancer, DDX17 promoted cell migration and invasion in vitro and in vivo, and its knockdown had the opposite effect. It regulated the miR-149-3p/CYBRD1 pathway to induce epithelial-mesenchymal transition and metastasis [4].

In conclusion, Ddx17 plays crucial roles in multiple biological processes and diseases. Gene knockout models, such as Ddx17-KO in HCC and Ddx17-cKO in heart failure, have revealed its importance in cancer metastasis and cardiac function maintenance, respectively. These findings suggest that Ddx17 could be a potential target for treating related diseases.