The purpose of this study was to investigate the effect of knockdown of the yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) on the migration and invasion of the rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and to preliminarily elucidate the mechanisms between YAP/TAZ and autophagy in the migration and invasion of RA-FLS. RA-FLS stable knockdown of YAP or TAZ was successfully established by using lentiviral-mediated gene knockdown techniques. Wound healing assay and Transwell assay were used to evaluate the effect of knockdown of YAP or TAZ on the migration and invasion of RA-FLS. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting assays were performed to examine the expression of indicated genes. The results showed that YAP and TAZ were upregulated in RA-FLS, and knockdown of YAP or TAZ inhibited the migration and invasion, reduced the expression of N-cadherin and Vimentin, and increased the accumulation of E-cadherin and β-catenin in RA-FLS. Our results also demonstrated that knockdown of YAP or TAZ promoted autophagy which increased the accumulation of LC3B-II and ULK1 and decreased the amount of SQSTM1/p62 in RA-FLS. Furthermore, our data displayed that inhibition of autophagy either with 3-MA or CQ can partially reverse the decrease of migration and invasion induced by YAP and TAZ knockdown in RA-FLS. Our experiments preliminarily revealed that YAP/TAZ and autophagy play important roles in the migration and invasion of RA-FLS, which might provide novel targets for the treatment of RA.

中文翻译：

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抑制YAP / TAZ通过调节自噬抑制类风湿关节炎中成纤维滑膜细胞的迁移和侵袭。

这项研究的目的是调查敲低是相关蛋白（YAP）和带有PDZ结合基序（TAZ）的转录共激活因子对类风湿关节炎成纤维细胞样滑膜细胞（RA-FLS）迁移和侵袭的影响并初步阐明YAP / TAZ与自噬之间RA-FLS迁移和侵袭的机制。通过使用慢病毒介导的基因敲除技术成功建立了RA-FLS对YAP或TAZ的稳定敲除。伤口愈合测定和Transwell测定用于评估YAP或TAZ的敲低对RA-FLS迁移和侵袭的影响。进行逆转录定量实时聚合酶链反应（RT-qPCR）和蛋白质印迹试验以检查指示基因的表达。RA-FLS中的β -catenin。我们的研究结果还表明，敲除YAP或TAZ可以促进自噬，从而增加LC- 3B-II和ULK1的积累，并减少RA-FLS中SQSTM1 / p62的含量。此外，我们的数据显示，用3-MA或CQ抑制自噬可以部分逆转RA-FLS中YAP和TAZ敲低引起的迁移和侵袭的减少。我们的实验初步表明，YAP / TAZ和自噬在RA-FLS的迁移和侵袭中起重要作用，这可能为RA的治疗提供新的靶点。