环状RNA-DOK1通过调节miR-122-5p/TNS1轴调控放射性脑损伤中小胶质细胞极化的机制研究

小胶质细胞激活是放射性脑损伤(RBI)发病中的关键一环。环状RNA(circular RNA)是一类新型非编码RNA，研究提示circRNA可作为微RNA(microRNA)海绵调控神经胶质细胞及其炎症类型转化，然而目前环状RNA在RBI发病过程中的调控机制仍为空白。前期研究中申请人基于基因测序、临床样本及功能分析发现miR-122-5p可内源性结合TNS1进而调控RBI中小胶质细胞激活，生物信息学分析提示circRNA-DOK1是潜在的miR-122-5p“海绵”，且circRNA-DOK1也被证实在放射后的小胶质细胞中显著下调。据此我们推测：调控circRNA-DOK1/miR-122-5p/TNS1轴可能缓解RBI中小胶质细胞激活及炎症级联损伤。本项目拟通过系列实验阐明circRNA-miRNA-信使RNA调控网络在小胶质细胞激活中的调控作用，旨在为RBI防治策略提供新思路。

Microglia activation and its cascade inflammatory injury is a key part of the pathogenesis of radiation-induced brain injury (RBI). It is suggested that circular RNA (circRNA) is a new type of non coding RNA involved in regulating glial cell and its inflammatory transformation via acting as miRNA sponge. However, the mechanism of circRNA regulation in the pathogenesis of RBI has not been illustrated yet. In the previous study, the applicant found that miR-122-5p could bind TNS1 endogenously to regulate the activation of microglia in RBI, based on gene sequencing, datas from the clinical samples and functional analysis. Moreover, the bioinformatics analysis suggested that circ-DOK1 was a potential sponge of miR-122-5p, and it was also confirmed to be significantly down regulated in microglia after radiation. Based on above findings, we speculated that the regulation of circ-DOK1/miR-122-5p/TNS1 axis might alleviate the microglial activation and inflammatory cascade damage in RBI. In conclusion, this project intends to clarify the regulatory role of circRNA-miRNA-messenger RNA regulatory network in microglia activation through a series of experiments, to provide new ideas for the prevention and treatment of RBI.