Expression and functional significance of the de novo purine synthesis enzyme PAICS gene in lung adenocarcinoma

doi:10.3877/cma.j.issn.1674-6902.2025.06.015

Abstract

Abstract:

Objective

To investigate the expression and functional significance of phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) in human lung adenocarcinoma and its mechanisms.

Methods

The GEO, GEPIA, and HPA databases were used to investigate the difference in expression of PAICS in lung adenocarcinoma compared with paracancerous tissues. The prognosis value of PAICS in patients with lung adenocarcinoma was evaluated by the GEPIA database and Kaplan-Meier Plotter platform. PAICS-associated co-expressed genes were obtained from the LinkedOmics database and used to perform gene ontology (GO) enrichment and KEGG enrichment analysis. The TIMER database was used to evaluate the relationship between PAICS and immune infiltration level of lung adenocarcinoma. Cultured A549 and H1299 cell lines were transfected with PAICS siRNA to investigate the effects of PAICS downregulation on the proliferation and migration of lung adenocarcinoma cell lines and the mRNA expression of CCNA2, CCNB1, CCNB2, and immune checkpoint gene PD-L1 in A549 and H1299.

Results

Multiple databases analysis revealed that PAICS expression was upregulated in patients with lung adenocarcinoma (P<0.001). High PAICS expression was negatively correlated with overall survival(P<0.001). The TIMER database revealed that the expression of PAICS in patients with lung adenocarcinoma were significantly and positively correlated with tumor cell purity (r= 0.13, P<0.01) but negatively correlated with B cells (r=-0.236, P<0.01), CD4⁺ T cells (r=-0.173, P<0.01), macrophages (r=-0.156, P<0.01), and dendritic cells (r=-0.131, P<0.01) in tumor microenvironment. GO enrichment and KEGG enrichment analyses indicated that PAICS-associated co-expressed genes were involved in the pathogenesis of lung adenocarcinoma through the regulation of cell cycle and cell mitosis. In cultured A549 and H1299 cell lines, PAICS siRNA transfection markedly attenuated the proliferation (P<0.01) and migration (P<0.01) of both cell lines and downregulated the expression of the genes encoding cyclin CCNA2 (P<0.05), CCNB1 (P<0.05), CCNB2 (P<0.05), and PD-L1 (P<0.05). In a xenograft mouse model transplanted with A549 cells, PAICS siRNA transfection markedly decreased the tumor size (P<0.05) and tumor weight (P<0.05).

Conclusion

PAICS plays a key role in the pathogenesis of lung adenocarcinoma. PAICS may serve as a prognostic indicator and potential target of lung adenocarcinoma, it with prospective clinical significance.

Key words: Lung adenocarcinoma, Phosphoribosylaminoimidazole succinocarboxamide synthetase, Immune infiltration, Cyclin

Linjuan Tang, Jinyue Wang, Xin Wang, Na Huang, Kai Yang. Expression and functional significance of the de novo purine synthesis enzyme PAICS gene in lung adenocarcinoma[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 942-948.

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