背景:DEAD-boxRNA解旋酶19A(DDX19A)在宫颈鳞状细胞癌中过度表达。然而,其在胃癌中的作用尚不清楚。本研究旨在探讨DDX19A在胃癌发生发展中的作用及机制。
方法:通过定量聚合酶链反应评估DDX19A在胃癌和癌旁组织中的表达,西方印迹,和免疫组织化学染色。用CCK8、平板集落形成、和Transwell迁移分析。用免疫印迹法研究了DDX19A在胃癌细胞中的具体作用机制,RNA结合蛋白免疫沉淀,mRNA半衰期检测,和核和细胞质RNA分离。
结果:DDX19A在胃癌中高表达,与胃癌的恶性临床病理特征和不良预后呈正相关。此外,DDX19A促进胃癌细胞增殖,迁移,和上皮-间质转化表型。机械上,DDX19A通过上调磷脂酰肌醇-3-激酶(PIK3CA)表达激活PI3K/AKT途径。此外,DDX19A与PIK3CAmRNA相互作用,稳定了它,并促进了它从原子核的出口。
结论:我们的研究揭示了一种新的机制,DDX19A通过增强PIK3CAmRNA的稳定性和核输出来促进胃癌细胞的增殖和迁移,从而激活PI3K/AKT途径。
BACKGROUND: DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer.
METHODS: The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation.
RESULTS: DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus.
CONCLUSIONS: Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.