RhoGDI2基因抑制膀胱癌转移涉及基因和信号通路的生物信息学分析

 目的 利用生物信息学方法探讨RhoGTP酶GDP解离抑制因子2 （rho GDP dissociation inhibitor 2，RhoGDI2） 基因抑制膀胱癌转移涉及的基因和信号通路。方法 从GEO datasets数据库搜索膀胱癌转移相关的全基因组表达谱芯片数据，使用GEO2R在线工具分析膀胱癌组织中RhoGDI2基因高表达组与低表达组之间的差异表达基因，再筛选出多组表达谱芯片数据中一致性上调或下调的基因，最后使用DAVID在线工具进行差异表达基因信号通路富集。结果 得到RhoGDI2基因在膀胱癌组织中高表达组和低表达组一致性高的差异表达基因，其中A2M、CORO1A、ENC1、FGD3为上调基因中一致性高的差异表达基因。通过基因信号通路富集分析得到膀胱癌组织中RhoGDI2基因调控的主要信号通路为Vav-RhoA-ROCK-MLC和Ras-Raf-MEK。结论 RhoGDI2基因可能通过Vav-RhoA-ROCK-MLC和Ras-Raf-MEK信号通路调节肌丝蛋白、细胞骨架以及细胞的增殖、分化等，进而抑制膀胱癌转移。

Bioinformatic analysis of genes and signaling pathways associated with RhoGDI2-inhibited bladder cancer metastasis

Objective This study used bioinformatics to examine the genes and signaling pathways associated with RhoGDP dissociation inhibitor 2（RhoGDI2） inhibits bladder cancer metastasis. Methods Six datasets from genomic microarray studies of patients with metastatic bladder cancer were downloaded from the Gene Expression Omnibus database. On-line GEO2R tools were used to screen for genes differentially expressed between individuals expressing low or high levels of RhoGDI2. On-line DAVID tools were used to map differentially expressed genes to signaling pathways. Result The genes A2M，CORO1A，ENC1，and FGD3 were expressed at higher levels in patients expressing high levels of RhoGDI2. RhoGDI2 appeared to influence the RhoA-ROCK-MLC and Ras-Raf- MEK signaling pathways to the greatest extent. Conclusion RhoGDI2 may act via the RhoA-ROCK-MLC and Ras-Raf-MEK pathways to regulate cytoskeleton， cell proliferation， differentiation and metastasis in bladder cancer.