CircRNA-microRNA相互对话调控GDF5/SIRT6信号通路在椎间盘退行性变中的作用及其机制研究

椎间盘退变（IDD）导致的下腰痛给社会带来沉重负担。前期研究证实IDD表现出GDF5/SIRT6通路过度抑制并发现其与异常高表达的微小RNA（miR-34a）有关。近年研究表明环状RNA（circRNA）-miRNA相互调控和动态平衡的紊乱在众多疾病发展中有重要作用，但IDD中环状RNA功能研究鲜有报道。我们前期通过高通量测序和生物信息学在髓核组织中发现一个新的以miR-34a为靶点的circRNA，暂称ciRS-34a。本课题拟通过临床标本、细胞实验、动物模型层面，采用RNA-FISH等技术，明确ciRS-34a-miR-34a相互调控，是否引起GDF5通路抑制，继而导致IDD，并运用特异性手段改变ciRS-34a表达，尝试缓解和逆转IDD，从而深入探讨ciRS-34a-miR-34a相互调控抑制GDF5/SIRT6通路在IDD发病机制中的作用,为IDD的临床早期诊断和治疗提供新的思路。

Low back pain resulted from intervertebral disc degeneration (IDD) brings heavy burden to the society. Previous studies confirmed that IDD demonstrated GDF5/SIRT6 pathway being excessively inhibited and this was found to be associated with abnormally high expression of microRNA(miR-34a). Recent studies have shown that circRNA-miRNA mutual regulation and dynamic balance disorder plays an important role in the development of many diseases. But there are very few reports on researches about functions of circRNA in IDD. In the early stage, we discovered a new circRNA targeting miR-34a (which is temporarily called ciRS-34a) in the nucleus pulposus by using high-throughput sequencing and bioinformatics. This study was to investigate whether ciRS-34a-miR-34a mutual regulation will result in GDF5 pathway inhibition and then lead to IDD by using clinical samples, cell experiments, animal models, as well as RNA-FISH and other technologies. And we used specificity ways to change the ciRS-34a expressions, and tried to remit and reverse IDD to make further research on the effects of ciRS-34a-miR-34a mutual regulations for GDF5/SIRT6 pathway inhibition in IDD pathogenesis, so as to provide new thoughts for IDD early clinical diagnosis and treatments.