RNA‑binding protein DAZAP1 promotes gastric cancer metastasis by enhancing NOTCH1 and JAG1 mRNA stability.

DAZ‑associated protein 1 (DAZAP1), an RNA‑binding protein and modulator of alternative splicing, participates in tumorigenesis. However, the potential oncogenic function and mechanism of DAZAP1 in gastric cancer (GC) are unknown. Gene expression analysis, including mRNA and protein level assessment by reverse transcription‑quantitative PCR and western blotting, respectively, immunofluorescence, immunohistochemistry, in situ hybridization assays, tissue microarray, RNA immunoprecipitation and sequencing and mRNA stability assay were performed, as well as colony formation, EdU, wound healing, migration and invasion assays of GC cells. DAZAP1 displayed a significant upregulation in GC cells and served as an oncogene, as demonstrated by its overexpression promoting colony formation, EdU incorporation, wound healing, migration and invasion, and its knockdown suppressing these malignant phenotypes. Additionally, DAZAP1 upregulation was positively correlated with tumor progression and poor survival in individuals with GC. Functionally, DAZAP overexpression promoted proliferation, epithelial‑mesenchymal transition (EMT) and migration/invasion of GC cells. Mechanistically, DAZAP1 physically bound NOTCH1 or JAG1 mRNA to regulate its stability. In addition, overexpression of DAZAP1 facilitated NOTCH1‑ and/or JAG1‑mediated migration via EMT in GC cells. Changes in NOTCH1 or JAG1 expression were positively correlated with DAZAP1 expression when DAZAP1 was silenced or enhanced in GC. Finally, DAZAP1 modulated the activation of the NOTCH/JAG1 signaling pathway. DAZAP1 expression facilitated migration/invasion and mediated the stabilization of NOTCH1 or JAG1 mRNA, suggesting they may participate in GC progression.