Department of Rheumatology and Immunology, Affiliated Jiujiang Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
Department of Neurology, Affiliated Jiujiang Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
Autoimmunity. 2022 Sep;55(6):360-370. doi: 10.1080/08916934.2022.2073590. Epub 2022 May 11.
Systemic lupus erythematosus (SLE) is defined as a multisystem autoimmune disease involving various organs, of which exact molecular mechanisms remain elusive. Here, we aimed to investigate a novel circular RNA (circRNA), circRACGAP1, abnormally expressed in SLE and explored its underlying regulatory network.
The expression patterns of circRACGAP1 were determined in patients diagnosed with SLE by using a qRT-PCR assay. Spearman correlation analysis was employed to evaluate the correlation between circRACGAP1 and clinicopathological variables in patients with SLE. Flow cytometry and TUNEL assays were subjected to assess the cell apoptosis. Nuclear-cytoplasmic fractionation and luciferase reporter assay was used to verify the circRACGAP1/miR-22-3p/PTEN axis. Western blot analysis was performed to measure the PTEN/AKT signalling-related proteins and apoptotic-related biomarkers.
Down-regulated circRACGAP1 was observed and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds) DNA, and complement C3 level in patients with SLE. Overexpression of circRACGAP1 significantly alleviated cell apoptosis in Jurkat cells within UVB exposure. Mechanistic investigation revealed that circRACGAP1 could serve as a sponge of miR-22-3p to regulate PTEN/AKT signalling.
Collectively, circRACGAP1 regulated the AKT signalling pathway binding to miR-22-3p in the progression of SLE, suggesting therapeutic targets for SLE treatment.
系统性红斑狼疮（SLE）被定义为一种涉及多个器官的多系统自身免疫性疾病，其确切的分子机制仍不清楚。在这里，我们旨在研究一种新型环状 RNA（circRNA），即 circRACGAP1，其在 SLE 中异常表达，并探讨其潜在的调控网络。
通过 qRT-PCR 检测确诊为 SLE 的患者中 circRACGAP1 的表达模式。采用 Spearman 相关性分析评估 circRACGAP1 与 SLE 患者临床病理变量之间的相关性。采用流式细胞术和 TUNEL 检测评估细胞凋亡。采用核质分离和荧光素酶报告基因检测验证 circRACGAP1/miR-22-3p/PTEN 轴。采用 Western blot 分析测定 PTEN/AKT 信号相关蛋白和凋亡相关生物标志物。
下调的 circRACGAP1 在 SLE 患者中观察到与系统性红斑狼疮疾病活动指数（SLEDAI）评分、抗双链（ds）DNA 和补体 C3 水平相关。circRACGAP1 的过表达显著减轻了 UVB 暴露下 Jurkat 细胞的细胞凋亡。机制研究表明，circRACGAP1 可以作为 miR-22-3p 的海绵来调节 PTEN/AKT 信号通路。
综上所述，circRACGAP1 通过与 miR-22-3p 结合调节 AKT 信号通路在 SLE 的进展中起作用，提示 SLE 治疗的治疗靶点。
