肿瘤转移是影响非小细胞肺癌预后最重要的因素之一。多项研究显示miRNA参与调控肺癌的侵袭和转移。我们前期研究首次发现过表达hsa-miR-623显著抑制非小细胞肺癌的生长、迁移和侵袭。近期预实验发现hsa-miR-623可能作用于核转运因子抑制Ku80分子进入细胞核,增加其在细胞质中的表达。Ku80核质定位的变化可能是hsa-miR-623抑制非小细胞肺癌转移的重要机制之一。本课题中，我们将利用体外实验和原位肺癌动物模型，系统地研究hsa-miR-623对Ku80进入细胞核的调控作用及分子机制；我们还将运用CRISPR/Base editor技术对Ku80核定位序列进行点突变，重点研究胞质型Ku80分子对非小细胞肺癌侵袭和转移的影响和分子机制，以及胞质型Ku80的临床意义及其与病人预后的关系。Hsa-miR-623或Ku80分子核质定位的改变将有可能成为抑制非小细胞肺癌侵袭和转移的新靶点。

Tumor metastasis is one of most important factors affecting the prognosis of non-small cell lung cancer (NSCLC). Many studies have shown that miRNAs are involved in lung cancer invasion and metastasis. Our previous study firstly indicated that overexpression of hsa-miR-623 significantly suppressed the NSCLC cell proliferation，migration and invasion. Further study indicated that hsa-miR-623 significantly inhibited the Ku80 protein nuclear import. We attempt to study the regulatory effect of hsa-miR-623 on Ku80 molecule nuclear translocation and its detailed molecular mechanisms. By using CRISPR/Base editor technology, we will induce the specific point mutation in nuclear localization sequence of Ku80 gene, and investigate the inhibitory effect of cytoplasmic Ku80 on NSCLC cell invasion and metastasis and related molecular mechanisms，as well as its clinical significance and prognosis prediction. Hsa-miR-623 or cytoplasmic Ku80 transmission will serve as the new target for suppression of NSCLC cell invasion and metastasis, and it may have important significance to improve the prognosis of patients with lung cancer.