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PDIA4 在肺腺癌中的潜在抗肿瘤特性。

Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.

机构信息

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea

出版信息

Anticancer Res. 2024 Oct;44(10):4309-4315. doi: 10.21873/anticanres.17260.

Abstract

BACKGROUND/AIM: Given the high frequency and mortality rate of lung cancer, diverse molecular studies have been undertaken to understand cancer pathophysiology and develop novel treatment strategies. The PDIA4 gene, which is involved in protein assembly and endoplasmic reticulum homeostasis, is overexpressed in various lung cancer subtypes. However, its exact function in lung adenocarcinoma (LUAD) remains elusive. The study aimed to investigate the role of PDIA4 in LUAD and explore its role as double-agent gene.

MATERIALS AND METHODS

PDIA4 expression was knocked out in A549 and LA-4 lung adenoma cells using the Crispr/Cas9 technology. Cell growth, migration, and apoptosis were analyzed in control and PDIA4-deficient cells.

RESULTS

PDIA4 deficiency resulted in increased cell growth, enhanced migration capacity, and greater resistance to apoptosis in both A549 and LA-4 lung cancer cells. Mechanistically, up-regulation of oxidative stress followed by NF-[Formula: see text]B activation may contribute to tumor-promoting effects observed upon PDIA4 silencing.

CONCLUSION

PDIA4 appears to function as a tumor suppressor in lung adenocarcinoma, suggesting that PDIA4 may act as a double-agent gene, with roles both on tumor suppression and promotion depending on the context.

摘要

背景/目的:由于肺癌的高发病率和死亡率,已经进行了各种分子研究,以了解癌症的病理生理学并开发新的治疗策略。PDIA4 基因参与蛋白质组装和内质网稳态,在各种肺癌亚型中过表达。然而,其在肺腺癌 (LUAD) 中的确切功能仍不清楚。本研究旨在探讨 PDIA4 在 LUAD 中的作用,并探索其作为双效基因的作用。

材料和方法

使用 Crispr/Cas9 技术敲除 A549 和 LA-4 肺腺癌细胞中的 PDIA4 表达。在对照和 PDIA4 缺陷细胞中分析细胞生长、迁移和凋亡。

结果

PDIA4 缺陷导致 A549 和 LA-4 肺癌细胞的细胞生长增加、迁移能力增强和凋亡抵抗增强。机制上,氧化应激的上调随后 NF-[Formula: see text]B 的激活可能导致 PDIA4 沉默观察到的促肿瘤作用。

结论

PDIA4 似乎在肺腺癌中作为肿瘤抑制因子发挥作用,表明 PDIA4 可能根据具体情况充当双效基因,既具有肿瘤抑制作用,又具有促进作用。

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