RND3对Snail1信号通路的作用及与人脑胶质母细胞瘤侵袭的关系

本项目重点研究小G蛋白RND3对Snail1信号通路的作用及与脑胶质母细胞瘤（GBM）侵袭的关系。RND3是Rho激酶抑制因子，可以抑制GBM的侵袭，但其分子机制尚不清楚。文献报道，RND3在肝癌中可以调节Snail1信号通路下游基因E-cadherin，而我们前期研究发现，RND3与Snail1蛋白结合，并降低Snail1蛋白表达量，Snail1蛋白是Snail1信号通路的关键蛋白，Snail1信号通路是调控GBM侵袭的关键信号通路。因此，本项目提出假说：RND3通过抑制Snail1信号通路，抑制GBM侵袭。本项目将从人脑GBM标本、胶质母细胞瘤细胞、基因敲除小鼠水平探讨RND3对Snail1信号通路的调控作用、具体分子机制以及RND3是否通过调控Snail1信号通路调控GBM侵袭。本项目有望增加对GBM侵袭分子机制的进一步理解，为GBM的治疗提供新靶点，并为以后的临床应用提供实验依据。

This proposal objects to investigate the regulation of RND3 (a small Rho GTPase) on Snail1 signaling and effect of RND3 on glioblastoma multiforme（GBM）invasion and associated molecular mechanism. RND3 is a endogenous inhibitor of Rho kinases, and can inhibit GBM cells invasion, however, the mechanism was unclear. studies have reported that RND3 regulates E-cadherin, whcih is the target gene of Snail1, in hepatocellular carcinoma. our previous study found that RND3 can bind Snail1 and decreased Snail1 protein expression level in GBM cells. As we known, Snail1 is critical for Snail signaling which is one of the most important signaling in GBM invasion. So we hypothesize that RND3 inhibits GBM cells invasion through inhibiting Snail1 signaling. We will detect the effect and mechanism of RND3 in regulating Snail1 signaling in human GBM samples, GBM cells and RND3 nude mice, we also will detect whether RND3 regulates Snail1 signaling is the critical mechanism of RND3 inhibiting GBM invasion. We believe that our work would strengthen the understanding of GBM mechanism,enrich experimental evidence for clinic GBM therapy and provide new molecular targeted for GBM gene therapy.