基于LINC00323介导的miRNA-611/MAPKAP1/VCAM-1信号通路探讨益气养阴填髓方抑制非小细胞肺癌血管生成的机制

血管生成与非小细胞肺癌(NSCLC)发生和发展关系密切。我们前期发现益气养阴填髓方通过影响NSCLC血管生成而抑制肿瘤生长，进一步利用LncRNA芯片分析发现益气养阴填髓方含药血清处理肺癌细胞A549，LINC00323表达明显下调，过表达或沉默LINC00323表达，能影响血管拟态形成，同时发现A549细胞来源的外泌体富含LINC00323，并能促进血管形成；生信分析结合实验验证LINC00323与miR-611作用，调控MAPKAP1表达。因此，我们提出“益气养阴填髓方通过调控LINC00323表达，影响癌细胞和血管内皮细胞miRNA-611/MAPKAP1/VCAM-1通路以抑制NSCLC血管生成”假说。本课题将利用细胞和气阴两虚型肺癌小鼠模型，通过体内和体外实验揭示益气养阴填髓方抑制NSCLC血管新生和血管拟态形成的机制。通过本项目研究，为“扶正培本法”临床治疗肺癌提供科学依据。

Angiogenesis is closely related to the occurrence and development of non-small cell lung cancer (NSCLC). We found earlier that yiqi yangyin tiansui formula inhibits tumor growth by affecting NSCLC angiogenesis, and further analyzed with LncRNA chip analysis to find that yiqi yangyin tiansui formula treats lung cancer A549 cells, and the expression of LINC00323 is significantly down-regulated. Overexpression or silencing the expression of LINC00323 can affect the formation of vascular mimicry. At the same time, it was found that exosomes derived from A549 cells were rich in LINC00323 and could promote angiogenesis. Biomarker analysis combined with experiments verified the effects of LINC00323 and miR-611 and regulated MAPKAP1 expression. Therefore, we propose the hypothesis that " yiqi yangyin tiansui formula affects the miRNA-611/MAPKAP1/VCAM-1 pathway of cancer cells and vascular endothelial cells to inhibit NSCLC angiogenesis by regulating the expression of LINC00323." In this study, we will use the cell and deficiency of qi and yin lung cancer mouse models to reveal the mechanism of yiqi yangyin tiansui formula inhibiting NSCLC angiogenesis and vascular mimicry in vivo and in vitro experiments. Through the research of this project, it will provide scientific basis for the clinical treatment of lung cancer by "strengthening body resistance and consolidating of origin therapy".