To investigate the roles of Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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.

中文翻译：

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受 Ca2+ 内流调节的 Circ-CAMTA1 抑制系统性红斑狼疮患者的丙酮酸羧化酶活性并调节 T 细胞功能


探讨 Ca2+ 内流调节的环状 RNA （circRNAs） 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与离子霉素共培养的 Jurkat 细胞中 circRNA 的表达谱，并使用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 细胞中进一步检查了鉴定的 Ca2+ 内流调节的 circRNA。使用转染和 RNA pull-down 测定研究特异性 circRNA 的生物学功能。经过验证，我们证实 circ-ERCC4 、 circ-NFATC2 、 circ-MYH10 、 circ-CAMTA1 、 circ-ASH1L 、 circ-SOCS7 和 circ-ASAP1 的表达水平在 Ca2 + 内流后 Jurkat 细胞中持续升高。SLE 患者 T 细胞中 circ-CAMTA1 、 circ-ASH1L 和 circ-ASAP1 的表达水平显著降低，在疾病活动度较高的 T 细胞中观察到的表达水平甚至更低。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活性。circ-CAMTA1 的过表达，而不是其线性形式的过表达，显着降低细胞外葡萄糖水平。此外，circ-CAMTA1 的表达增加，而不是其线性形式，降低了 miR-181c-5p 的表达，导致 IL-2 分泌增加。三种 Ca2+ 内流调节的 circ-RNA — circ-CAMTA1 、 circ-ASH1L 和 circ-ASAP1 — 在 SLE 患者的 T 细胞中显着减少，并与疾病活动相关。IFN-α 抑制 circ-CAMTA1 的表达，circ-CAMTA1 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，Ca²⁺ 内流调节的 circ-CAMTA1 调节了 SLE 患者的 T 细胞功能。