Intracellular and exosomal miR-101-3p regulated by METTL14 confers Gefitinib sensitivity in NSCLC.

Gefitinib Resistance (GR) is a frequent occurrence for non-small cell lung cancer (NSCLC). Here, we aim to explore a novel miR-101-3p shuttled by NSCLC cells in the growth and metastasis of NSCLC cells. Real-time PCR was performed to assess the level of miR-101-3p in cells and exosomes derived from the NSCLC cells. Effect of miR-101-3p on cell proliferation, metastasis and gefitinib sensitivity was then detected. Instinctively, METTL14 expression level was detected, which was positively related to that of miR-101-3p. Function of METTL14 on cell proliferation and metastasis was also investigated. High level of exosomal and intracellular miR-101-3p is correlated with better gefitinib response. miR-101-3p inhibited NSCLC cell proliferation and migration. In terms of mechanism, METTL14 endow NSCLC cells with gefitinib sensitivity via intracellular and exosomal miR-101-3p, leading to modulating of GSK-3β/Akt pathway. Collectively, this study indicated that restored METTL14/miR-101-3p confers gefitinib sensitivity in GR NSCLC by targeting GSK-3β/Akt pathway, indicating METTL14/miR-101-3p may act as a potential biomarker and therapeutic target for gefitinib response in NSCLC.