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摘要细胞外基质(extracellular matrix,ECM)重塑是癌细胞迁移的关键步骤.本研究基于乳腺癌组织的基因表达谱数据,采用系统生物学方法推测乳腺癌转移中Runx2对细胞外基质重塑的调节机制.采用相关性分析程序分析49例乳腺原发癌和15例淋巴结转移癌组织的基因表达谱数据,筛选与Runx2呈相关性表达的基因,结果得到与ECM重塑相关的候选基因52个,包括ECM成分11个,ECM降解酶及其抑制剂8个,细胞信号分子33个.利用转录调节因子结合序列数据库搜索候选基因启动子区的Runx2结合模序,筛选其中Runx2转录调控的ECM重塑相关基因,并判断可能调节Runx2的上游信号分子;文献检索实验证实的与Runx2有相互调节关系的基因,并基于Runx2上游调控信号分子和下游转录调节基因的分析,构建得到以Runx2为中心的ECM重塑的生物学调控网络.WNT和TGF/BMPs是启动Runx2表达的主要信号通路,Runx2通过转录调节ECM组分、ECM降解酶及其抑制剂和信号分子调节ECM重塑,促进癌细胞完成转移的生物学过程.
Abstract Extracellular matrix (ECM) remodeling is a key step of cancer cell migration.In this study, based on the gene expression profiling data of breast cancer tissues, we systematically deduced that Runx2 remodeling extracellular matrix in breast cancer metastasis Regulatory mechanism.The correlation analysis program was used to analyze the gene expression profiles of 49 cases of primary breast cancer and 15 cases of lymph node metastasis and to screen the genes related to Runx2 expression.Results 52 candidate genes related to ECM remodeling , Including 11 ECM components, 8 ECM degrading enzymes and their inhibitors, and 33 cell signaling molecules.Using the transcription regulatory factor and sequence database to search for the Runx2 binding motif in the promoter region of candidate genes, the ECM weight of Runx2 transcriptional regulation Plasticity-related genes, and determine the possible upstream Runx2 signaling molecules; literature search experiments confirmed Runx2 has a relationship between the regulation of genes, and based on Runx2 upstream regulatory signal molecules and downstream transcriptional regulation gene analysis to build to Runx2 as the center ECM remodeling biological regulatory networks.WNT and TGF / BMPs is the main pathway to start Runx2 expression, Runx2 through transcription ECM components, ECM degrading enzymes and their inhibitors and signaling molecules regulating ECM remodeling to promote the complete transfer of the biological processes of cancer cells.