DDX19A promotes gastric cancer cell proliferation and migration by activating the PI3K/AKT pathway

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-08-03 DOI:10.1186/s12935-024-03448-5

Yu Cheng, Yanjie Lu, Jing Xue, Xuemei Wang, Lili Zhou, Yu Luo, Yuhong Li

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Abstract

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. 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. 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. 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.

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DDX19A 通过激活 PI3K/AKT 通路促进胃癌细胞增殖和迁移

DEAD-box RNA 螺旋酶 19 A（DDX19A）在宫颈鳞状细胞癌中过度表达。然而，它在胃癌中的作用仍不清楚。本研究旨在探讨DDX19A在胃癌发生中的作用及其内在机制。通过定量聚合酶链式反应、Western 印迹和免疫组化染色评估了 DDX19A 在胃癌和癌旁组织中的表达。通过CCK8、平板集落形成和Transwell迁移试验确定了DDX19A在胃癌中的生物学功能。利用 Western 印迹、RNA 结合蛋白免疫沉淀、mRNA 半衰期检测、核和细胞质 RNA 分离等方法研究了 DDX19A 在胃癌细胞中的特异性机制。DDX19A在胃癌中高表达，与恶性临床病理特征和不良预后呈正相关。此外，DDX19A还能促进胃癌细胞的增殖、迁移和上皮-间质转化表型。从机理上讲，DDX19A通过上调磷脂酰肌醇-3-激酶（PIK3CA）的表达激活了PI3K/AKT通路。此外，DDX19A 与 PIK3CA mRNA 相互作用，使其稳定，并促进其从细胞核中输出。我们的研究揭示了一种新的机制，即DDX19A通过增强PIK3CA mRNA的稳定性和核输出，从而激活PI3K/AKT通路，促进胃癌细胞的增殖和迁移。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.