Unlocking the role of EIF5A: A potential diagnostic marker regulating the cell cycle and showing negative correlation with immune infiltration in lung adenocarcinoma

Background: Despite EIF5A upregulation related to tumor progression in LUAD (lung adenocarcinoma), the underlying mechanisms remain elusive. In addition, there are few comprehensive analyses of EIF5A in LUAD.Methods: We investigated the EIF5A expression level in LUAD patients using data from the TCGA and GEO databases. We employed qRT-PCR and western blot to verify EIF5A expression in cell lines, while immunohistochemistry was utilized for clinical sample analysis. We analyzed EIF5A expression in tumor-infiltrating immune cells using the TISCH database and assessed its association with immune infiltration in LUAD using the ESTI-MATE R package. Bioinformatics approaches were developed to discover the EIF5A-related genes and explore EIF5A potential mechanisms in LUAD. Proliferation ability was verified through CCK-8, clone formation, and EdU assays, while flow cytometry assessed apoptosis and cell cycle. Western blot was used to detect the expression of pathway-related proteins.Results: EIF5A was significantly upregulated in LUAD. Moreover, we constructed a MAZ-hsa-miR-424-3p-EIF5A transcriptional network. We explored the potential mechanism of EIF5A in LUAD and further investigated the cAMP signaling pathway and the cell cycle. Finally, we proved that EIF5A silencing induced G1/S Cell Cycle arrest, promoted apoptosis, and inhibited proliferation via the cAMP/PKA/CREB signaling pathway.Conclusion: EIF5A serves as a prognostic biomarker with a negative correlation to immune infiltrates in LUAD. It regulated the cell cycle in LUAD by inhibiting the cAMP/PKA/CREB signaling pathway.

Automated summary

In this study, EIF5A was found to be significantly upregulated in LUAD. We constructed a MAZ-hsa-miR-424-3p-EIF5A transcriptional network and investigated the potential mechanism of EIF5A in LUAD. By exploring the cAMP signaling pathway and the cell cycle, we demonstrated that EIF5A regulates the cell cycle in LUAD by inhibiting the cAMP/PKA/CREB signaling pathway, and it is negatively correlated with immune infiltrates in LUAD.