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DDX19A通过激活PI3K/AKT信号通路促进胃癌细胞的增殖和迁移。

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

作者信息

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

机构信息

Department of Pathology, Chengde Medical College, Chengde, Hebei Province, China.

Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei Province, China.

出版信息

Cancer Cell Int. 2024 Aug 3;24(1):272. doi: 10.1186/s12935-024-03448-5.

DOI:10.1186/s12935-024-03448-5
PMID:39097730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297674/
Abstract

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.

摘要

背景

DEAD盒RNA解旋酶19A(DDX19A)在宫颈鳞状细胞癌中过表达。然而,其在胃癌中的作用仍不清楚。本研究旨在探讨DDX19A在胃癌发生发展中的作用及潜在机制。

方法

通过定量聚合酶链反应、蛋白质免疫印迹法和免疫组织化学染色评估DDX19A在胃癌组织和癌旁组织中的表达。使用CCK8、平板集落形成和Transwell迁移试验确定DDX19A在胃癌中的生物学功能。采用蛋白质免疫印迹法、RNA结合蛋白免疫沉淀法、mRNA半衰期检测法以及细胞核和细胞质RNA分离法研究DDX19A在胃癌细胞中的具体机制。

结果

DDX19A在胃癌中高表达,且与恶性临床病理特征及不良预后呈正相关。此外,DDX19A促进胃癌细胞增殖、迁移以及上皮-间质转化表型。机制上,DDX19A通过上调磷脂酰肌醇-3-激酶(PIK3CA)表达激活PI3K/AKT通路。此外,DDX19A与PIK3CA mRNA相互作用,使其稳定,并促进其从细胞核输出。

结论

我们的研究揭示了一种新机制,即DDX19A通过增强PIK3CA mRNA的稳定性和细胞核输出,从而激活PI3K/AKT通路,促进胃癌细胞的增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fbc/11297674/44ddf1f625be/12935_2024_3448_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fbc/11297674/34a3785e9c66/12935_2024_3448_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fbc/11297674/44ddf1f625be/12935_2024_3448_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fbc/11297674/25f559dd46a0/12935_2024_3448_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fbc/11297674/34a3785e9c66/12935_2024_3448_Fig5_HTML.jpg
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