抑癌基因Nm23-H1主要定位于胞浆，其在胞核内的作用研究尚少。我们前期研究显示胞核Nm23-H1与非小细胞肺癌术后复发转移显著相关，能促进肺癌细胞增殖和侵袭，但机制尚不清楚。课题组进一步研究显示胞核Nm23-H1能显著上调肺癌侵袭转移相关基因CYP24A1的表达；生物信息学预测AP-1为CYP24A1的潜在转录因子。已有研究证明胞核Nm23-H1能与AP-1结合并参与转录调控。基于此，我们提出假说：胞核Nm23-H1通过与AP-1结合参与转录调控，上调CYP24A1促进非小细胞肺癌侵袭转移。本项目拟应用胞核过表达Nm23-H1的A549细胞系为工具，综合运用细胞生物学、分子生物学、生物信息学等研究手段，深入研究胞核Nm23-H1调控 CYP24A1促进非小细胞肺癌侵袭转移的分子机制。本研究将为寻找新的抗非小细胞肺癌侵袭转移的治疗靶点提供思路。

Nm23-H1 is mainly located in the cytoplasm, and its role in the nucleus is not clear. Our previous studies showed that the expression of nm23-H1 in nuclear was significantly related to the recurrence and metastasis of non-small cell lung cancer (NSCLC), which promoted the proliferation and invasion of lung cancer cells, but the mechanism was not clear.Our preliminary study showed that nuclear localization of Nm23-H1 significantly upregulated the expression of CYP24A1, and could bind to AP-1, a potential transcription factor of CYP24A1, which played a role in transcription regulation of CYP24A1.Based on this, we present a hypothesis that Nm23-H1 upregulates CYP24A1 and promotes the invasion and metastasis of lung cancer cells through its interaction with AP-1.This project intends to use Nm23-H1 nuclear localization in NSCLC cells to explore the role of Nm23-H1 nuclear localization in up-regulation of CYP24A1 on the recurrence and metastasis of lung cancer and the mechanism by multi-methods in cell biology, molecular biology and bioinformation. This study will provide ideas for finding new therapeutic targets against invasion and metastasis of NSCLC.