hsa_circ_0000417介导miR-6756-5p靶向调控AR信号通路在尿道下裂发生中的作用机制研究

尿道下裂是小儿泌尿系最常见的先天性畸形之一，circRNA被发现参与到泌尿系疾病进展中，但其在尿道下裂发生中的作用尚不清楚。 高通量测序表明，hsa_circ_0000417在尿道下裂包皮组织中显著下调，干扰hsa_circ_0000417后，HFF-1细胞增殖、凋亡增加。临床样本定量结果显示，hsa_circ_0000417的表达与AR表达显著正相关，且生信分析发现miR-6756-5p与二者均存在多个结合位点。由此，我们首次提出：hsa_circ_0000417介导miR-6756-5p上调AR以抑制尿道下裂进程。本课题拟以 hsa_circ_0000417为研究目标，采用Chip-Seq、RNA-pull down、RIP等技术手段阐明 hsa_circ_0000417通过“吸附”miR-6756-5p调控AR及其下游信号通路参与尿道下裂的发生发展的机制，为尿道下裂防治提供新思路。

Hypospadias is one of the most common congenital malformation in the pediatric urology population, circRNA plays an important role in the reproduction,but the it’s role in hypospasias remains unclear. High-throughput RNA-seq was performed to assess circRNA expression profiles in 3 healthy and hypospadias foreskin tissue and hsa_circ_0000417 was decreased significantly in hypospadias.When we Knocked hsa_circ_0000417 down in HFF-1 cells, the proliferation and apoptosis was increased. Correlation analysis showed that the expression of hsa_circ_0000417 was positively correlated with AR in clinical samples, and bioinformatics analysis revealed that miR-6756-5p has multiple binding sites with both of them. Therefore, we proposed that hsa_circ_0000417 as a sponge of miR-6756-5p to up regulated AR and inhibits the pathogenesis of hypospadias for the first time. We focus on hsa_circ_0000417 in our research, Firstly, we will figure out the circRNA involved in phenotype of hypospadias in vivo and in vitro. Further more, we will answer whether hsa_circ_0000417 regulating the pathogenesis of hypospadias and elucidate the mechanism of has_circ_0000417 regulated AR and its signaling pathways by “absorbing”has-miR-6756-5p. providing new evidence and new ideas for the prevention and treatment of hypospadias.