miR214调控SUFU表达在肺腺癌上皮间充质转化中的作用及机制研究

EMT are involved in the invasion and metastasis of lung adenocarcinoma,and miRNAs play an important role in the process of EMT. Our previous studies showed that miR214 was upregulated during EMT process,and increased expression of miR214 promoted EMT in lung adenocarcinoma. Evidence suggested that miR214 can inhibit translation of SUFU, an inhibitor of SUFU hedgehog pathway,which leads to EMT transition. Based on the previous results and evidence from literature, we propose: miR214 promoted EMT process through inhibition of SUFU gene,ultimately involved in the metastasis of lung adenocarcinoma. In this project, lentivirus-mediated miR214/miR214 inhibitor transfected lung adenocarcinoma cells were used to observe the role of miR214 in EMT process; shRNA and other technology were uesed to verify the miR214 targeted inhibition of SUFU thus contributing to promte EMT in lung adenocarcinoma.Clinical samples to further verify the correlation between miR214 and SUFU, and its relationship with clinical outcome. The project will not only elucidate the specific molecular mechanism of miR214 promoting EMT process in lung adenocarcinoma, but also provides new scientific evidence for the prevention and treatment of metastasis in lung adenocarcinoma.

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。本项目组前期发现：miR214在肺腺癌EMT过程中表达上调，且具有促进肺腺癌细胞EMT的作用；SUFU为miR214潜在靶分子，在肺腺癌细胞中miR214和SUFU表达呈负相关。基于SUFU的生物学功能和Hedgehog信号通路在EMT中的作用，我们推测：miR214通过抑制SUFU表达，从而充分激活Gli介导的Hedgehog信号通路，最终促进肺腺癌细胞EMT。拟在前期实验基础上，建立高表达和低表达miR214肺腺癌细胞株，明确miR214在肺腺癌EMT中的作用；采用shRNA等技术阐明miR214通过抑制SUFU进而促进肺腺癌EMT的分子机制；临床标本分析miR214与SUFU表达相关性，及其与EMT和转移的相关性。通过本项目，不但能完善肺腺癌细胞EMT的分子机制，而且也将为临床侵袭转移的防治提供新思路。

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。本项目组前期发现：miR214 在肺腺癌 EMT 过程中表达上调，且具有促进肺腺癌细胞 EMT 的作用；SUFU 为 miR214 潜在靶分子，在肺腺癌细胞中 miR214 和 SUFU 表达呈负相关。基于 SUFU 的生物学功能和 Hedgehog 信号通路在EMT 中的作用，我们推测：miR214 通过抑制 SUFU 表达，从而充分激活 Gli 介导的 Hedgehog 信号通路，最终促进肺腺癌细胞 EMT。本项目在前期工作的基础上，建立了高表达和低表达 miR214 肺腺癌细胞株，进一步明确了miR214 在肺腺癌 EMT 中的作用；并通过网络预测及实验验证等方法证实miR214 通过抑制 SUFU 进而促进肺腺癌 EMT的分子机制；并在临床标本中同样发现了miR-214表达与靶基因SUFU 在表达上存在显著负相关，及其与 EMT 和转移的相关性。通过本项目，不但能完善肺腺癌细胞 EMT 的分子机制，而且也将为临床侵袭转移的防治提供新思路。 已发表相关SCI论文2篇，影响因子均大于5, 招收培养硕士、博士研究生各2名，且获得“重庆市优秀博士论文”及“全军优秀博士论文”各1篇。