Purpose

Rheumatoid arthritis (RA) is a commonly diagnosed systemic autoimmune disease. Aberrant expression of long non-coding RNAs (lncRNAs) is closely linked to the development of RA. This study was conducted to explore the functions of the lncRNA LINC01197 in RA progression.

Methods

Differentially expressed lncRNAs/microRNAs/mRNAs in patients with RA were analyzed using RNA microarrays. A mouse model with RA was established and RA-fibroblast-like synoviocytes (RA-FLS) were acquired for in vitro experiments. The function of LINC01197 in inflammation and RA progression in mice and its role in the viability of RA-FLS were determined by experiments involving its overexpression or suppression. The sub-cellular localization of LINC01197 was determined and the downstream molecules involved in LINC01197-mediated events were identified.

Results

LINC01197 was poorly expressed in the synovial tissues in the RA model mice. Overexpression of LINC01197 reduced RA severity in mice and inhibited proliferation and inflammatory responses as well as promoted apoptosis in RA-FLS. Online predictions and dual luciferase reporter gene assays suggested that LINC01197 could bind to miR-150 and further regulate THBS2 expression. LINC01197 promoted THBS2 expression through miR-150 sponging and inactivated the TLR4/NF-κB signaling pathway, thus alleviating RA inflammation.

Conclusion

The current study suggested that LINC01197 sponged miR-150 to promote THBS2 expression, leading to TLR4/NF-κB inactivation, and ameliorated RA inflammation. These findings may offer new insights into RA treatment.

中文翻译：

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通过microRNA-150 / THBS2轴，长链非编码RNA LINC01197在类风湿关节炎的炎症中的抑制作用。

目的

类风湿关节炎（RA）是一种常见的全身性自身免疫性疾病。长非编码RNA（lncRNA）的异常表达与RA的发展密切相关。进行该研究以探索lncRNA LINC01197在RA进展中的功能。

方法

使用RNA芯片分析RA患者中差异表达的lncRNA / microRNA / mRNA。建立具有RA的小鼠模型，并获得RA成纤维样滑膜细胞（RA-FLS）进行体外实验。LINC01197在小鼠炎症和RA进展中的功能及其在RA-FLS活力中的作用通过涉及过表达或抑制的实验确定。确定了LINC01197的亚细胞定位，并确定了参与LINC01197介导的事件的下游分子。

结果

LINC01197在RA模型小鼠的滑膜组织中表达较差。LINC01197的过表达降低了小鼠的RA严重程度，并抑制了RA-FLS的增殖和炎症反应以及促进了细胞凋亡。在线预测和双重荧光素酶报告基因检测表明，LINC01197可以与miR-150结合并进一步调节THBS2的表达。LINC01197通过miR-150海绵促进THBS2表达，并灭活TLR4 /NF-κB信号通路，从而减轻RA炎症。

结论

目前的研究表明，LINC01197使miR-150发挥作用，以促进THBS2表达，从而导致TLR4 /NF-κB失活，并减轻RA炎症。这些发现可能为RA治疗提供新的见解。