Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
Chongqing International Institute for Immunology, 13 Tianchi Avenue, Banan District, Chongqing, 401320, People's Republic of China.
J Transl Med. 2022 Nov 26;20(1):547. doi: 10.1186/s12967-022-03748-2.
Accumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE.
Quantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570.
The results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis.
Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.
越来越多的证据表明环状 RNA（circRNA）在系统性红斑狼疮（SLE）中具有重要作用。然而，关于 circRNA 在 SLE 发病机制中的详细机制和作用知之甚少。
采用实时定量 PCR 检测 SLE 患者外周血单个核细胞中 circLOC101928570 和 miR-150-5p 的水平。通过过表达和敲低实验评估 circLOC101928570 的作用。荧光原位杂交、RNA 免疫沉淀、荧光素酶报告基因检测、Western blot、流式细胞术分析和酶联免疫吸附试验用于研究 circLOC101928570 功能的分子机制。
结果表明，circLOC101928570 在 SLE 中显著下调，与系统性红斑狼疮疾病活动指数相关。功能上，circLOC101928570 作为 miR-150-5p 的海绵，减轻了其对靶基因 c-myb 的抑制作用，从而调节免疫炎症反应的激活。circLOC101928570 敲低增强了细胞凋亡。此外，circLOC101928570 通过直接调节 miR-150-5p/c-myb 轴促进 IL2RA 的转录水平。
综上所述，我们的研究结果表明 circLOC101928570 在 SLE 中发挥了关键作用。circLOC101928570 的下调通过 miR-150-5p/c-myb/IL2RA 轴抑制 SLE 的进展。我们的研究结果表明 circLOC101928570 可作为 SLE 诊断和治疗的潜在生物标志物。
