Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Rheumatology and Immunology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.
Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Mol Immunol. 2020 Sep;125:131-139. doi: 10.1016/j.molimm.2020.07.004. Epub 2020 Jul 13.
Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of various types of cancers by serving as microRNA sponges to regulate the expression of target genes. Although in-depth studies of circRNAs have been conducted, their functional and pathological significance in autoimmune diseases, including rheumatoid arthritis (RA), remains unclear. Our previous study verified that hsa_circ_0088036 (circ0088036) is significantly elevated in peripheral blood mononuclear cells from patients with RA. The present study aimed to explore the roles of circ0088036 in the pathogenesis of RA. The circ0088036/miR-140-3p/silent information regulator 1 (SIRT 1) axis was predicted by bioinformatics tools. Circ0088036 was found to be aberrantly upregulated in fibroblast-like synoviocytes (FLSs) in RA compared with FLSs in osteoarthritis (OA). Functionally, upregulated circ0088036 promoted the proliferation and migration of RA-FLSs. Mechanistically, circ0088036 acted as a miR-140-3p sponge to upregulate SIRT 1 expression, subsequently promoting RA progression. In conclusion, this study revealed that circ0088036 may play an essential role in promoting synovial pathogenesis via the circ0088036/miR-140-3p/SIRT 1 axis in RA, providing new insight into circRNAs during RA progression.
环状 RNA(circRNAs)已被证明通过作为 microRNA 海绵来调节靶基因的表达,在各种类型癌症的发生和发展中发挥关键作用。尽管已经对 circRNAs 进行了深入研究,但它们在自身免疫性疾病(包括类风湿关节炎(RA))中的功能和病理意义仍不清楚。我们之前的研究证实 hsa_circ_0088036(circ0088036)在 RA 患者的外周血单核细胞中显著升高。本研究旨在探讨 circ0088036 在 RA 发病机制中的作用。通过生物信息学工具预测了 circ0088036/miR-140-3p/沉默信息调节因子 1(SIRT 1)轴。与骨关节炎(OA)中的成纤维样滑膜细胞(FLSs)相比,RA 中的 FLSs 中 circ0088036 异常上调。功能上,上调的 circ0088036 促进了 RA-FLSs 的增殖和迁移。机制上,circ0088036 作为 miR-140-3p 的海绵,上调 SIRT 1 的表达,进而促进 RA 的进展。总之,本研究表明 circ0088036 可能通过 circ0088036/miR-140-3p/SIRT 1 轴在 RA 中发挥重要作用,促进滑膜发病机制,为 circRNAs 在 RA 进展过程中的作用提供了新的见解。