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Archive > Volume 30 Issue 4 > 2023,30(4):309-317. DOI:10.3872/j.issn.1007-385X.2023.04.005 Prev Next
Basic Research
Low STING expression in lung adenocarcinoma promotes tumor progression via inhibiting endoplasmic reticulum stress
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Abstract:
Objective: To analyze the expression of stimulator of interferon gene (STING) in lung adenocarcinoma and the correlation between clinical features of lung adenocarcinoma patients and the expression of STING, and to investigate the association of STING with endoplasmic reticulum (ER) stress, and the functions and mechanisms of STING in regulating the progression of lung adenocarcinoma. Methods: The expression of STING at pan-cancer level was analyzed by using TIMER database. The expression of STING in lung adenocarcinoma tissue and the correlation between STING expression and clinical features of lung adenocarcinoma patients were explored by using UALCAN and HPA database. The correlation between STING expression and overall survival (OS) rates of lung adenocarcinoma patients was analyzed by using Kaplan-Meier survival function. Analysis of the co-expressed genes with STING was performed based on the expression profile data of lung adenocarcinoma from LinkedOmics database. GO function and KEGG pathway analyses were conducted to investigate the differential expressed genes (DEGs) of STING, and GSEA was performed to explore the potential pathways through which STING might regulate lung adenocarcinoma. The STING agonist, diABZI, and the ER stress inhibitor, TUDCA, were used to treat lung adenocarcinoma cell lines, A549 and H460, and the expressions of STING and ER stress-associated molecules were examined by qPCR and Western blotting, and the cell vitality was detected by CCK-8 assays. Results: The expressions of STING in lung adenocarcinoma tissues and cells were significantly lower than those in normal lung tissues (all P<0.01). The 5-year OS rates of lung adenocarcinoma patients with high STING expression were notably higher than those of low-expression patients (P<0.01), and the expression of STING were closely correlated with clinical characteristics of the lung adenocarcinoma patients, such as age and gender (all P<0.01). High STING expression was enriched in pathways, such as exogenous antigen processing and presentation in lung adenocarcinoma (all P<0.01). The use of STING agonist significantly induced ER stress in lung adenocarcinoma (P<0.05). STING activation significantly lowered the vitality of lung adenocarcinoma cells (all P<0.01), which could be partly reversed by using the ER stress inhibitor (P<0.05). Conclusion: The expression of STING is downregulated in lung adenocarcinoma, which is closely associated with worse clinical prognosis of the lung adenocarcinoma patients. STING could inhibit lung adenocarcinoma cell vitality by inducing ER stress.
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