Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin, Chiayi, 62247, Taiwan.
Department of Life Science, Institute of Molecular Biology, National Chung Cheng University, Minxiong, Chiayi, Taiwan.
Arthritis Res Ther. 2024 Oct 29;26(1):185. doi: 10.1186/s13075-024-03422-6.
To investigate the roles of Ca influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE).
The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay.
After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion.
Three Ca influx-regulated circ-RNAs-circ-CAMTA1, circ-ASH1L, and circ-ASAP1 -were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE.
研究钙内流调控的环状 RNA（circRNA）在系统性红斑狼疮（SLE）患者 T 细胞中的作用。
通过下一代测序分析共培养有无离子霉素的 Jurkat 细胞中的 circRNA 表达谱，并通过实时聚合酶链反应进行验证。在 42 例 SLE 患者和 23 例健康对照者的 T 细胞中进一步检测鉴定的钙内流调控 circRNA。使用转染和 RNA 下拉实验研究特定 circRNA 的生物学功能。
验证后，我们确认钙内流后 Jurkat 细胞中 circ-ERCC4、circ-NFATC2、circ-MYH10、circ-CAMTA1、circ-ASH1L、circ-SOCS7 和 circ-ASAP1 的表达水平持续升高。SLE 患者 T 细胞中 circ-CAMTA1、circ-ASH1L 和 circ-ASAP1 的表达水平明显降低，且疾病活动度较高者表达水平更低。发现干扰素（IFN）-α抑制 circ-CAMTA1 的表达。circ-CAMTA1 与丙酮酸羧化酶结合并抑制其生物学活性。circ-CAMTA1 的过表达（而非其线性形式）显著降低细胞外葡萄糖水平。此外，circ-CAMTA1 的表达增加（而非其线性形式）降低了 miR-181c-5p 的表达，导致 IL-2 分泌增加。
SLE 患者 T 细胞中三种钙内流调控的 circRNA（circ-CAMTA1、circ-ASH1L 和 circ-ASAP1）表达明显降低，与疾病活动度相关。IFN-α抑制 circ-CAMTA1 的表达，其与丙酮酸羧化酶相互作用，抑制其活性，影响葡萄糖代谢，增加 IL-2 分泌。这些发现表明钙内流调控的 circ-CAMTA1 调节 SLE 患者 T 细胞功能。
