获得性耐药是EGFR TKI在非小细胞肺癌临床应用的瓶颈和亟待解决的难题。上皮间质转化（EMT）和miRNA在多种肿瘤的恶性表型包括耐药、转移和肿瘤干细胞的调控中发挥重要作用。EMT和miRNA之间存在交互作用，但其在TKI获得性耐药中的作用和机制尚未阐明。前期从miRNA芯片数据筛选出的25种候选miRNA中首次发现hsa-miR-483-3p和EMT有交互作用，而miR-483-3p在肺癌发生发展中的作用未见报道。前期还首次发现整合素b3是miR-483-3p的靶点之一；miR-483-3p能在体外逆转肺癌细胞EMT、增加耐药肺癌细胞对TKI的敏感性和减弱肺癌细胞干性（stemness）。拟进一步在细胞、动物、人体三个层面对miR-483-3p和EMT交互作用及机制、miR-483-3p信号通路能否成为对抗EGFR TKI获得性耐药和转移的靶点进行研究，为肺癌靶向药物的研发提供新思路。

Acquired resistance is the bottleneck that restricts the efficacy of EGFR TKI for non-small cell lung cancer (NSCLC) and strategies to overcome it are urgently needed. Epithelial-mesenchymal transition (EMT) and microRNA (miRNA) both play an important role in the regulation of malignant phenotype including chemotherapy resistance, metastasis and cancer stem cells in many cancer types. Studies have shown that there is interplay between EMT and miRNA, the roles of which in acquired EGFR TKI resistance remain unknown. Our preliminary data showed for the first time that hsa-miR-483-3p was associated with EMT phenotype among 25 candidate miRNAs screened by miRNA microarray analysis. So far, there is no report studying the role of miR-483-3p in tumorigenesis and development of lung cancer in the literature. Our preliminary data also showed for the first time that integrin beta 3 was one of miR-483-3p’s targets and miR-483-3p reversed EMT, increased EGFR TKI sensitivity and reduced stemness in EGFR TKI-resistant NSCLC cells in vitro. This project has intended to use molecular and cellular techniques to further investigate the interplay between miR-483-3p and EMT and underlying mechanisms and the potential of miR-483-3p and downstream signaling pathways as novel therapeutic targets against acquired EGFR TKI resistance and metastasis in NSCLC in cell, animal and human models. Hopefully, the results will provide new ideas on developing new targeted lung cancer drugs.