MS4A3 Promotes the Chemosensitivity of Lung Cancer via THAP1/EGFR Pathways.

ABSTRACT

MS4A3 functions as a tumor suppressor in multiple cancer types. However, the roles of MS4A3 in lung cancer are still unknown. Therefore, this study aims to investigate the potentials of MS4A3 in lung cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine mRNA expression. CCK-8 and colony formation assay are conducted to determine cell proliferation. Tube formation assay is performed to determine angiogenesis. Flow cytometry is used to determine cell apoptosis. JASPAR is used to analyze the binding motif of THAP1. Luciferase and ChIP assay are conducted to verify whether MS4A3 can interact with THAP1 to transcriptionally inactivate EGFR. The results showed that MS4A3 is downregulated in non-small-cell lung cancer (NSCLC) patients, which predicts poor clinical outcomes of NSCLC patients. Overexpressed MS4A3 enhances the chemosensitivity of NSCLC cells to osimertinib, whereas MS4A3 knockdown exerts the opposite effects. MS4A3 suppresses the proliferation and angiogenesis and promotes the apoptosis of NSCLC cells. Moreover, MS4A3 upregulates apoptosis-related THAP1 to inactivate EGFR. However, THAP1 knockdown attenuates the effects of MS4A3 and promotes the malignant behavior of NSCLC cells. In conclusion, MS4A3 functions as an anti-tumor gene in NSCLC. MS4A3/THAP1/EGFR signaling enhances the chemosensitivity of lung cancer to EGFR tyrosine kinase inhibitor (TKI).