Lin28是体细胞重要的重编程因子，通过与let7形成双重负反馈调节通路（即Lin28/let7回路）促进肿瘤的发生发展。文献报道Lin28在肺癌组织中过表达，并与不良预后相关。我们前期研究中利用FGF1和IGF1建立条件3D培养体系，在体外高效富集并扩增了肺癌干细胞，同时发现肺癌干细胞中Lin28/let7回路关键基因异常表达，并伴有MAPK通路激活。但Lin28/let7回路和MAPK通路对肺癌干细胞的调控机制尚不明确。本研究中，我们拟从细胞、组织和动物模型多角度探讨Lin28/let7回路和MAPK通路的交互作用，提出“Lin28/let7/MAPK”级联通路，从细胞增殖、凋亡、周期等多层次探讨Lin28/let7/MAPK通路在肺癌干细胞扩增中的作用机制。本研究将进一步补充和完善肿瘤干细胞调控网络，并试图筛选出针对肺癌干细胞的潜在治疗靶点，为该领域的后续研究和临床治疗奠定基础。

Lin28 is an important reprogramming factor for human somatic cells. Lin28 and let7 form a double negative feedback regulatory pathway (i.e., the Lin28/let7 loop), which promotes tumorigenesis and tumor progression. Overexpression of Lin28 has been reported in lung cancer and is correlated with poor outcomes. In our previous studies, we applied FGF1 and IGF1 to establish the conditional 3D culture system to enrich and amplify lung cancer stem cells in vitro. What’s more, we found that the expression levels of the key genes in the Lin28/let7 loop were abnormal and the MAPK signaling pathway was activated in lung cancer stem cells. However, the regulatory mechanisms of the Lin28/let7 loop and the MAPK signaling pathway in lung cancer stem cells are not clear yet. In this study, we will focus on the interaction between the Lin28/let7 loop and the MAPK signaling pathway and propose a hypothesis that the "Lin28/let7/MAPK" cascade signaling pathway regulates the amplification of lung cancer stem cells both in vitro and in vivo via influencing cell proliferation, cell apoptosis, cell cycle, etc. This study will further supplement the regulatory network of cancer stem cells and screen the potential therapeutic targets for lung cancer treatment, as well as provide the solid experimental evidences for the further researches and clinical applications in this field.