肺腺癌(LAC)侵袭转移过程中普遍存在抑癌基因WIF1功能异常，DNMTs、PRC2介导的WIF1甲基化与此密切相关。我们前期发现：与WIF1存在特殊位置关系的linc-WIF1-1可与DNMTs、PRC2相互作用并影响WIF1基因功能，但DNMTs和PRC2是分别还是共同参与Linc-WIF1-1调控WIF1尚不明确。为此，我们提出假说：Linc-WIF1-1可通过招募DNMTs和/或PRC2介导WIF1甲基化促进LAC侵袭转移。为验证该假说，我们将通过人肺腺癌细胞株、免疫缺陷小鼠转移模型，采用腺病毒载体转染、RNA干扰、RIP、Co-IP等手段，从组织、细胞及动物整体水平探讨Linc-WIF1-1在LAC侵袭转移中的作用，明确Linc-WIF1-1招募DNMTs和/或PRC2介导WIF1甲基化的调控机制。本研究将为揭示LAC侵袭转移的机制奠定理论基础，为LAC诊治、预后评估提供新思路。

Dysfunction of tumor suppressor gene WIF1 is a generally existent phenomenon in the invasion and metastasis of lung adenocarcinoma (LAC). WIF1 methylation mediated by DNMTs,PRC2 is closely related to this phenomenon. In pre experiment, we found a new lncRNA(linc-WIF1-1,which has special position adjacent to WIF1 on the same chromosome) interacted with DNMTs, PRC2 and affected WIF1 gene function. But, whether DNMTs and PRC2 participate in this modulating process respectively or jointly is still unclear. To this end, we put forward the hypothesis: Linc-WIF1-1 can recruit DNMTs and/or PRC2 to mediate WIF1 hypermethylation, WIF1 gene transcription and functional inactivation of WIF1, so as to promote the invasion and metastasis of LAC. To test this hypothesis, we will perform adenovirus vector transfection, RNA interference, RIP, ChIP, Co-IP and other means in lung adenocarcinoma cell lines A549, SPCA1 and NOD/SCID immunodeficient mice metastasis model, to explore the regulation mechanism of Linc-WIF1-1 recruitment of DNMTs and/or PRC2 in WIF1 methylation and its role in invasion and metastasis of LAC. This study carried out on the molecular, cell, tissue and whole animal levels will identify the role of Linc-WIF1-1 in invasion and metastasis of LAC, and will reveal the regulation mechanism of WIF1 methylation mediated by Linc-WIF1-1 recruitment of DNMTs and/or PRC2. This study will shed lights on research of invasion and metastasis of LAC from a new perspective, and will provide the theoretic foundation for the diagnosis, therapy and evaluation of prognosis of LAC.