本申请将着重研究circular RNA (circRNA) 通过竞争性结合miRNA对癌症转移相关基因的调控影响。我们前期研究发现癌症转移抑制基因受到miRNA的调控并在卵巢癌转移样本中发生差异表达。本申请中我们将结合前期研究结果，利用TCGA泛癌症基因组学数据及收集到的癌症转移促进基因和抑制基因，构建circRNA与miRNA相互作用介导的癌症转移基因调控网络及生物信息学网络分析平台。通过系统网络分析，探索癌症转移中circRNA对转移促进基因和抑制基因的调控机制，发现重要的circRNA及其影响的miRNA和癌症转移基因，检测这些circRNA在结直肠癌肿瘤组织中的表达水平，阐明circRNA在癌症转移中的效应途径，并探讨circRNA与患者临床参数之间的关系及与患者生存预后的相关性。

By focusing on the circRNA-based cancer metastasis regulatory network, we aim to identify the key circRNA and miRNA-mediated regulatory motifs, which may are potential diagnostic or predictive biomarkers in cancers..This proposal has three aims: .Aim 1) Large-scale inference of competing endogenous circRNAs as the sponge to neutralize the inhibitory effects of miRNAs by using TCGA pan-cancer data and construction of circRNA and miRNA-mediated human cancer regulatory network (CMN);.Aim 2) Focusing on cancer metastasis, we will intersect our curated metastasis promoting and suppressing genes to the CMNs from Aim 1 to construct circRNA and miRNA-mediated human cancer metastasis regulatory network (CMMN) and to prioritize the key circRNAs from the metastasis-specific regulatory networks based on topological importance;.Aim 3) For proof-of-concept, we will test the top candidate circRNAs and their relevant miRNAs and targeting metastasis-related genes in colorectal cancer tissue samples. By further exploration of the relationship between the key circRNAs and the clinical information such as survival periods, we will build an effective strategy to develop the circRNA-based biomarkers for diagnosis in colorectal cancer.