Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Chongqing International Institute for Immunology, Chongqing, China.
Arthritis Res Ther. 2022 Feb 4;24(1):37. doi: 10.1186/s13075-022-02732-x.
Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE METHODS: Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE.
Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2).
The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.
某些 circRNAs 可用作确定系统性红斑狼疮（SLE）发展和/或严重程度的风险的生物标志物，其在基因表达调控中的新功能促使我们研究其在 SLE 中的作用。
采用 qRT-PCR、RNA 免疫沉淀（RIP）、下拉、双荧光素酶报告基因检测、RNA 干扰和细胞转染、RNA 荧光原位杂交、Western blot 和质谱等实验方法，评估 circGARS（hsa_circRNA_0009000）的免疫功能，并确定 circGARS 促进 SLE 进展的机制。
我们的研究结果表明，circGARS 在 SLE 中显著上调，并与临床病理特征相关。circGARS 直接与 microRNA-19a（miR-19a）结合。功能上，circGARS 通过下调肿瘤坏死因子α诱导蛋白 3（A20）的表达，介导由核因子-κB（NF-κB）通路调控的免疫反应的激活，作为负反馈机制。此外，miR-19a 通过下调 YTH N6-甲基腺苷 RNA 结合蛋白 2（YTHDF2）的表达来调节 A20（TNFAIP3）的降解。
circGARS 海绵吸附 miR-19a 来调节 YTHDF2 的表达，通过 A20/NF-κB 轴促进 SLE 进展，并且可能作为一种独立的生物标志物来帮助治疗 SLE 患者。
