带有表皮生长因子受体（EGFR）突变的非小细胞肺癌(NSCLC)患者最初对酪氨酸激酶抑制剂（TKIs）有良好的临床反应。不幸的是，主要由于基因改变，包括肝细胞生长因子受体（MET）扩增及其异常活性，迅速出现了耐药性。有助于肿瘤MET异常表达的RNA转录后修饰在很大程度上尚未得到研究，其中包括microRNAs的腺嘌呤到肌酸核苷(A-to-I) RNA编辑。在多种癌症中，包括NSCLC，在miR-411-5p的5号位置减少了A-to-I修饰。在本研究中，通过癌症相关基因表达分析，我们评估了编辑的miR-411-5p对NSCLC细胞系的影响。我们发现编辑的miR-411-5p直接靶向MET，并负面影响丝裂原活化蛋白激酶（MAPKs）通路。考虑到MAPKs通路在TKIs耐药性中的主导作用，我们生成了对TK抑制剂具有耐药性的NSCLC EGFR突变细胞系，并评估了miR-411-5p编辑过表达的效应。我们发现，编辑的miR-411-5p减少了增殖并诱导细胞凋亡，在NSCLC耐药细胞中促进EGFR TKIs的反应。 © 2023. 作者授权Springer Nature Limited独家发布。

Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation have an initial favorable clinical response to the tyrosine kinase inhibitors (TKIs). Unfortunately, rapid resistance occurs mainly because of genetic alterations, including amplification of the hepatocyte growth factor receptor (MET) and its abnormal activity. The RNA post-transcriptional modifications that contribute to aberrant expression of MET in cancer are largely under-investigated and among them is the adenosine-to-inosine (A-to-I) RNA editing of microRNAs. A reduction of A-to-I editing in position 5 of miR-411-5p has been identified in several cancers, including NSCLC. In this study, thanks to cancer-associated gene expression analysis, we assessed the effect of the edited miR-411-5p on NSCLC cell lines. We found that edited miR-411-5p directly targets MET and negatively affects the mitogen-activated protein kinases (MAPKs) pathway. Considering the predominant role of the MAPKs pathway on TKIs resistance, we generated NSCLC EGFR mutated cell lines resistant to TK inhibitors and evaluated the effect of edited miR-411-5p overexpression. We found that the edited miR-411-5p reduces proliferation and induces apoptosis, promoting EGFR TKIs response in NSCLC-resistant cells.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.