MS4A3 promotes the chemosensitivity of lung cancer via THAP1/EGFR pathways

Abstract

MS4A3 functions as a tumor suppressor in multi-type cancer. However, the role of MS4A3 in lung cancer is still unknown. Therefore, this study aims to investigate the potential of MS4A3 in lung cancer. RT-qPCR is carried out to detect 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 calculate apoptosis rates. JASPAR is used to determine the binding motif of THAP1. Luciferase and ChIP assay are conducted to verify that MS4A3 can interact with THAP1 to transcriptionally inactivate EGFR. 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. Moreover, 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. 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).