申请者前期研究证实miR-150在NSCLC细胞和组织中高表达，发现miR-150抑制NSCLC细胞的自噬体成熟，自噬体成熟关键基因EPG5是miR-150的靶标。据此提出“在NSCLC中，miR-150异常高表达，通过靶向抑制EPG5的表达，抑制自噬体成熟，导致ROS等有害物质积累，促进肺癌发生”的科学假说。为此，本项目将从细胞、动物和临床样本三个层面研究miR-150是否通过靶向EPG5抑制自噬、促进NSCLC发生。通过项目研究，揭示miR-150抑制自噬促进NSCLC发生的作用及其机制；证实miR-150通过靶向EPG5抑制自噬体成熟，发现miR-150抑制自噬的新机制；明确临床NSCLC样本中miR-150/EPG5/自噬通路存在异常，为miR-150高表达的NSCLC的诊治提供靶标。

Our previous studies confirmed that miR-150 was highly expressed in NSCLC cells and tissues. We further found that miR-150 blocked the fusion of autophagosomes with lysosomes (autophagosome maturation), and that EPG5, which is the key regulator in autophagosome maturation, was the novel target of miR-150. Thus, we propose the hypothesis that upregulated miR-150 in NSCLC inhibits autophagosome maturation via targeting EPG5 and causes the accumulation of harmful substances such as variety of proteins and reactive oxygen species (ROS), which contributes to the oncogenesis of lung cancer. Therefore, this study will be explore the role of miR-150 in blocking autophagosome maturation via targeting EPG5 to promote NSCLC oncogenesis from three levels of cells, animal models and clinical samples. This research will reveal the important function and novel molecular mechanism of miR-150 in promoting NSCLC through inhibition of autophagosome maturation by targeting EPG5. Furthermore, it will verify that miR-150/EPG5/pathway is aberrant in clinical samples of NSCLC, which will provide a foundation for the prevention and treatment of NSCLC associated with miR-150 overexpression.