Clinical research data show that gefitinib greatly improves the progression‐free survival of patients, so it is used in advanced non‐small cell lung cancer patients with EGFR mutation. However, some patients with EGFR sensitive mutations do not have good effects on initial gefitinib treatment, and this mechanism is rarely studied. METTL3, a part of N6‐adenosine‐methyltransferase, has been reported to play an important role in a variety of tumours. In this study, we found that METTL3 is up‐regulated in gefitinib‐resistant tissues compared to gefitinib‐sensitive tissues. Cell function experiments have proved that under the treatment of gefitinib, METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells. Mechanistic studies have shown that METTL3 combines with MET and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. Therefore, our research shows that METTL3 can be used as a molecular marker to predict the efficacy of EGFR‐TKI therapy in patients, and METTL3 may be a potential therapeutic target.

中文翻译：

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RNA甲基转移酶METTL3与MET联合调控肺腺癌PI3K/AKT通路诱导吉非替尼内在耐药

临床研究数据表明，吉非替尼大大提高了患者的无进展生存期，因此用于EGFR突变的晚期非小细胞肺癌患者。然而，一些EGFR敏感突变的患者在初始吉非替尼治疗中效果不佳，这种机制很少被研究。据报道，METTL3 是 N6-腺苷甲基转移酶的一部分，在多种肿瘤中发挥重要作用。在这项研究中，我们发现与吉非替尼敏感组织相比，METTL3 在吉非替尼耐药组织中上调。细胞功能实验证明，在吉非替尼治疗下，METTL3敲低促进肺癌细胞凋亡，抑制肺癌细胞增殖。机理研究表明，METTL3 与 MET 结合，导致 PI3K/AKT 信号通路被操纵，从而影响肺癌细胞对吉非替尼的敏感性。因此，我们的研究表明，METTL3可以作为预测EGFR-TKI治疗患者疗效的分子标志物，METTL3可能是一个潜在的治疗靶点。