Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma

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-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.