结直肠癌的发生是一个多因素参与的复杂生物学过程，其中miRNAs通过参与基因转录后调控在结直肠癌的发生发展中起关键作用。近期研究报道，竞争性内源RNA(ceRNAs)作为miRNAs的上游调节分子，通过竞争性抑制miRNAs与靶基因mRNA3'UTR的结合，发挥对miRNAs和靶基因的调控作用。前期工作中我们应用生物信息学和GEO数据库分析发现YES1和VAMP4作为ceRNA与抑癌基因SMAD4在肿瘤组织表达水平呈正相关性，并初步实验证明二者可下调SMAD4水平。本项目将进一步明确ceRNA对SMAD4 3'UTR的调节，以及在此过程中miRNAs所起的作用，探讨ceRNAs对TGFβ/Smad信号通路及肿瘤细胞表型的影响，研究上述分子在结直肠癌组织表达的相关性。以期阐明以ceRNAs→miRNAs→SMAD4调控网络为核心的表观遗传学分子机制，从而为结直肠癌的防治提供新的潜在干预靶点。

The development of colorectal cancer is a complex biological process, in which a variety of factors are invloved. miRNAs play an important role in the development of colorectal cancer by regulating target RNA transcripts post-transcriptionally. Most recently, many studies have identified that "competing endogenous RNAs'' (ceRNAs), as upstream molecules regulating miRNAs, could bind to and compete for the same pool of miRNAs with target mRNA 3'UTR.As a result, ceRNAs regulate the level of miRNAs and target genes..Our previous study identified that the level of YES1 and VAMP4, as the predicted ceRNA for tumor suppressor SMAD4, was significantly positively correlated with SMAD4 transcript in cancer tissues by bioinformatics and GEO database analysis.Our results demonstrated that YES1 and VAMP4 down-regulate SMAD4 on mRNA and protein level. .This project is to verify the regulation of ceRNA to SMAD4 3'UTR，to explore the function of miRNAs in this process, to investigate the effects of ceRNAs on the phenotype of cancer cells by TGFβ/Smad signaling pathway, and to detect the association of YES1, VAMP4,and SMAD4 expression in colorectal cancer tissues. Taken together, Our study will demonstrate the epigenetics molecular mechanism of ceRNAs→miRNAs→SMAD4 network, and provide potential new targets for the prevention and therapy to patients with colorectal cancer.