TRIB2具有癌基因样作用，在肺腺癌组织中表达明显增高。抑制TRIB2表达能诱发肺腺癌细胞凋亡。miRNAs参与了肺癌基因表达、细胞转移和浸润等过程；有关TGF-β1通路miRNA的研究已成为肺腺癌研究的热点之一。 近期研究中，我们建立了移植肺腺癌细胞的小鼠模型，发现反义核酸能有效抑制癌基因miRNA表达，进而抑制肺腺癌细胞在小鼠体内增殖。本项目在课题组研究miRNAs的基础上，发现miR-206能抑制肺腺癌细胞Smad3及癌基因trib2表达，而Smad3是TGF-β1通路的重要因子，提示miR-206可能参与了TGF-β1通路及肺腺癌的发病过程。以此为出发点，我们将深入研究TRIB2及miR-206等是否参与了TGF-β1通路、TRIB2表达是否受Smad3因子的调节，探讨TGF-β1通路相关miRNA调节癌基因trib2在肺腺癌发病中的作用，为肺腺癌临床治疗及药物设计提供新靶点。

TRIB2, acting as one oncogene, is over-expressed in lung adenocarcinoma tissues. Inhibition of TRIB2 expression can lead to apoptosis of lung adenocarcinoma cells. miRNAs play important roles in the procession of gene expression, cell migration and invasion. It becomes a hot research topic to study the TGF-β1-pathway-related miRNAs. In recent study, we established the nude mice model xenografted with A549 cells and found that antisense RNA could inhibit lung adenocarcinoma cell proliferation in vivo by suppressing the expression of oncogenic miRNA. Based on the previous study of miRNAs, our results showed that miR-206 could inhibit expression of Smad3 and trib2 in lung adenocarcinoma cells, and Smad3 is one of the important factors in TGF-β1 pathway, which indicated that miR-206 might attend TGF-β1 pathway. In this research, we will further study whether both TRIB2 and miR-206 attend TGF-β1 pathway, and whether TRIB2 expression is regulated by Smad3. We will also investigate the roles of trib2 expression regulated by TGF-β1-pathway-related-miRNAs in pathogeny of lung adenocarcinoma. This project will provide new gene targets for therapy of lung adenocarcinoma and drug design.