miR-218负相调控ECOP和ROBO1信号对肺腺癌上皮间充质化的影响及其机制研究

EMT is a key link in the invasion and metastasis of lung adenocarcinoma cells, miRNA play an important role in the EMT process. In our preliminary experiments, we found that miR218 inhibited activation of NF-κB in lung adenocarcinoma cells, and miR-218 also obtained a significant reduction in lung adenocarcinoma EMT. Previous studies showed that miR218 can block the ECOP and Robo1-induced NF-κB activation, ECOP and Robo1 may be miR218 target genes. According to fact that ECOP and Robo1 signaling pathway play a critical role in the EMT-based, we hypothesized that miR218 inhibited ECOP and Robo1 expression and signaling transduction, consequently blocking the activation of NF-κB-mediated lung adenocarcinoma EMT. The project intends to preliminary experiments, based on the establishment of high and low expression of miR218 expression in lung adenocarcinoma cell lines, clarify the role of miR218 in EMT in lung adenocarcinoma, and using shRNA technology to clarify miR218 role by inhibiting the ECOP and Robo1 thereby blocking lung adenocarcinoma molecular mechanisms of EMT; clinical specimens analyzed miR218 and ECOP and Robo1 expression correlated with EMT and its metastasis. Through this project, not only can improve lung adenocarcinoma cell EMT molecular mechanism, but will also provide new ideas and target for the prevention and treatment of clinical invasion and metastasis.

EMT是肺腺癌细胞侵袭转移的关键环节，miRNA 在EMT过程中发挥重要作用。预实验发现miR218 在肺腺癌细胞中抑制NF-κB激活，且诱导肺腺癌EMT后miR218表达显著降低。研究报道miR218可阻断ECOP和Robo1介导NF-κB激活，ECOP和Robo1可能为miR218靶基因。基于ECOP和Robo1信号通路在EMT中的作用，我们推测：miR218通过抑制ECOP和Robo1信号激活，阻断NF-κB激活介导的肺腺癌EMT。本项目拟在前期实验基础上，建立高表达和低表达miR218肺腺癌细胞株，明确miR218在肺腺癌EMT中的作用；采用shRNA等技术阐明miR218通过抑制ECOP和Robo1进而阻断肺腺癌EMT的分子机制；临床标本分析miR218与ECOP和Robo1表达相关性，及其与EMT、恶化、转移的相关性。本项目可为肺腺癌侵袭、转移提供新理论基础和药物治疗靶点。

EMT是肺腺癌细胞侵袭转移的关键环节，miRNA 在EMT过程中发挥重要作用。预实验发现miR218 在肺腺癌细胞中抑制NF-κB激活，且诱导肺腺癌EMT后miR218表达显著降低。研究报道miR218可阻断ECOP和Robo1介导NF-κB激活，ECOP和Robo1可能为miR218靶基因。基于ECOP和Robo1信号通路在EMT中的作用，我们推测：miR218通过抑制ECOP和Robo1信号激活，阻断NF-κB激活介导的肺腺癌EMT。本项目建立了高表达和低表达miR218肺腺癌细胞株，明确miR218在肺腺癌EMT中的作用；采用shRNA等技术阐明miR218通过抑制ECOP和Robo1进而阻断肺腺癌EMT的分子机制；能够抑制NF-κB信号通路的激活；临床标本分析miR218与ECOP和Robo1表达成负相关性，及其与EMT、恶化、转移的相关性。本项目可为肺腺癌侵袭、转移提供新理论基础和药物治疗靶点。