1. Academic Validation
  2. RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma

RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma

  • J Cell Mol Med. 2021 Mar;25(5):2418-2425. doi: 10.1111/jcmm.16114.
Fangyan Gao 1 Qianqian Wang 1 Chang Zhang 2 3 Chen Zhang 1 Tianyu Qu 1 Jingya Zhang 1 Jifu Wei 4 Renhua Guo 1
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 3 Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China.
  • 4 Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract

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.

Keywords

METTL3; RNA methyltransferase; gefitinib resistance; lung adenocarcinoma.

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