Phenylalanyl-tRNA synthetase subunit beta downregulation by spi1 proto-oncogene modulates lung adenocarcinoma...

Phenylalanyl-tRNA synthetase subunit beta (FARSB) is implicated in the progression of multiple cancers and represents a potential therapeutic target. However, its role in lung adenocarcinoma (LUAD) progression and the immune microenvironment remains poorly understood, warranting further investigation into its regulatory mechanisms.

We conducted bioinformatics analyses to investigate the expression levels of FARSB in LUAD, identify enriched pathways, and assess its correlation with patient prognosis and CD8 + T cell infiltration. Bioinformatics analysis was also used to explore the transcriptional repression of FARSB by spi1 proto-oncogene (SPI1) and to validate the targeting relationship between SPI1 and FARSB. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was utilized to measure the mRNA expression of FARSB and SPI1, while western blot was used to detect the expression of FARSB, SPI1, programmed death-ligand 1 (PD-L1), and related signaling pathway proteins. Functional assays were performed, including CCK-8 assay for cell viability, EdU incorporation for cell proliferation, and flow cytometry for apoptosis analysis. Carboxyfluorescein succinimidyl ester (CFSE) staining was used to analyze CD8 + T cell proliferation, and flow cytometry was used to assess the expression of cytokines interferon-gamma (IFN-γ), Granzyme B (GZMB), and tumor necrosis factor-alpha (TNF-α).

FARSB expression was significantly upregulated in LUAD tissues and cells, and it inhibited CD8 + T cell infiltration. Mechanistically, FARSB activated the mammalian target of rapamycin (mTOR) signaling pathway, enhancing LUAD cell viability, proliferation, and anti-apoptotic capabilities, consequently promoting CD8 + T cell exhaustion. The transcription factor SPI1 repressed FARSB expression, thus inhibiting LUAD progression and promoting CD8 + T cell anti-tumor immunity.

SPI1 downregulated FARSB expression through transcriptional repression, thereby blocking the mTOR signaling pathway and suppressing LUAD progression and promoting CD8 + T cell anti-tumor immunity.