前期研究发现，RA-FLS中的NUTM2A-AS1、TIMP1和TIMP3表达显著下调，而miR-17和miR-206明显上调；过表达NUTM2A-AS1、TIMP1或TIMP3的RA-FLS迁移和侵袭能力明显下降，而过表达miR-17或miR-206的RA-FLS迁移和侵袭能力明显增强。生物信息学方法关联分析发现，NUTM2A-AS1可能通过miR-17和miR-206分别调控TIMP1和TIMP3的表达。本课题拟在前期工作基础上，采用基因过表达、干扰表达或敲除等方法，以RA患者关节滑膜组织、原代培养的RA-FLS和RA-FLS细胞株以及SCID-HuRAg小鼠模型为研究对象，阐明NUTM2A-AS1通过miR-17和miR-206分别调控TIMP1和TIMP3的表达影响RA-FLS的迁移和侵袭，进一步导致软骨的侵蚀和破坏的机制。本研究可能为发展相应的治疗RA措施提供理论依据和新靶标。

Our previous studies showed that the expression of NUTM2A-AS1, TIMP1 and TIMP3 in RA-FLS were significantly down-regulated, while miR-17 and miR-206 were significantly up-regulated. Further studies demonstrated that overexpression of NUTM2A-AS1, TIMP1 or TIMP3 in RA-FLS obviously decreased the migration and invasion, and overexpression of miR-17 or miR-206 in RA-FLS enhanced the cellular migratory and invasive ability. Bioinformatics analysis demonstrated that NUTM2A-AS1 could regulate the expression of TIMP1 and TIMP3 via miR-17 and miR-206, respectively. Based on the previous work, we will perform gene overexpression, gene knockdown or knockout to conduct a series of researches, in which the joint synovial tissues in patients with RA, primary cultured RA-FLS, RA-FLS cell strain and SCID-HuRAg mouse model will be taken as the research objects. We aim to clarify the mechanism of NUTM2A-AS1 regulating the expression of TIMP1/3 via miR-17 and miR-206 respectively to affect the migration and invasion of RA-FLS, and further contribute to the erosion and damage of cartilage. This study may provide theoretical basis and novel targets for the development of the treatment measures of RA.