The Traditional of Inner Mongolia Medical University Affiliated Hospital.
Crit Rev Eukaryot Gene Expr. 2024;34(8):1-11. doi: 10.1615/CritRevEukaryotGeneExpr.2024053662.
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).
MS4A3 在多种癌症类型中作为肿瘤抑制因子发挥作用。然而，MS4A3 在肺癌中的作用尚不清楚。因此，本研究旨在探讨 MS4A3 在肺癌中的潜力。采用逆转录定量聚合酶链反应（RT-qPCR）测定 mRNA 表达。CCK-8 和集落形成实验用于检测细胞增殖。管形成实验用于检测血管生成。流式细胞术用于检测细胞凋亡。JASPAR 用于分析 THAP1 的结合基序。荧光素酶和 ChIP 实验用于验证 MS4A3 是否可以与 THAP1 相互作用以转录失活 EGFR。结果表明，MS4A3 在非小细胞肺癌（NSCLC）患者中下调，这预示着 NSCLC 患者的临床预后不良。过表达 MS4A3 增强了 NSCLC 细胞对奥希替尼的化疗敏感性，而 MS4A3 敲低则产生相反的效果。MS4A3 抑制 NSCLC 细胞的增殖和血管生成，促进其凋亡。此外，MS4A3 上调与凋亡相关的 THAP1 以失活 EGFR。然而，THAP1 敲低减弱了 MS4A3 的作用，并促进了 NSCLC 细胞的恶性行为。总之，MS4A3 在 NSCLC 中作为一种抑癌基因发挥作用。MS4A3/THAP1/EGFR 信号增强了肺癌对 EGFR 酪氨酸激酶抑制剂（TKI）的化疗敏感性。
