circRNA_000681与miR-126构成ceRNA网络靶向调控内皮细胞凋亡与深静脉血栓形成的作用和机制

深静脉血栓（DVT）危害大，发病机制不清，内皮细胞凋亡在DVT发生中起关键作用。我们前期发现：过表达miR-126可抑制DVT大鼠内皮细胞凋亡，减少血栓形成，但miR-126在转录后的上下游调控关系并不清楚。基于应答原件序列配对，我们利用starBase和CIRCpedia，预测环状RNA circ_000681可能通ceRNA机制，充当miR-126的海绵，解除miR-126对靶基因的抑制，调控内皮细胞凋亡与DVT。在前期基础上，本项目拟在临床、动物和细胞中，通过circRNA芯片、DAVID和RT-PCR确定DVT内皮细胞差异表达的circRNA；利用RNA-FISH和Luciferase Assay进行circRNA/miR-126互作分析；利用RNA-RIP和RNA-ChIP构建circRNA/miR-126/mRNA/protein调控网络，为DVT的分子调控和靶向治疗提供依据。

Deep vein thrombosis (DVT) is of great harm and unclear pathogenesis, in which apoptosis of endothelial cells play a crucila role. Our previous research showed that: over-expressed miR-126 in DVT rat model could reduce endothelial cells apoptosis and decrease thrombosis formation, whereas the regulating relation of miR-126 is still unknown. Based on MREs pairing rules, we adopt starBase and CIRCpedia to predict that circ_000681 may act as a sponge of miR-126 through ceRNA mechanism, removing the inhibition of miR-126 on target genes and regulating endothelial cells apoptosis and DVT. Based on previous research, the current project plans in vivo and vitro, to screen and validate differentially expressed circRNA through circRNA microarray, DAVID and RT-PCR; analyze circRNA/miRNA interaction using RNA-FISH and Luciferase Assay; construct circRNA/miRNA/mRNA/protein regulation network by RNA-RIP and RNA-ChIP, providing basis of molecular regulation and targeted therapy for DVT.