Polycystic ovarian syndrome (PCOS) is considered to be one of the most prevalent endocrine disorders affecting women of reproductive age. CiRS-126, an innovative circular microRNA, has previously been proven to be a promising miR-21 sponge. However, a proper understanding of the impact of ciRS-126 on PCOS is needed. Circular RNA (CiRS) profiles were initially evaluated in ovarian cortex samples obtained from 18 women with PCOS as well from 9 women without PCOS. Insulin-induced ovarian granulosa cells isolated from mice were utilized for the functional study. CiRS microarray analysis and quantitative real-time PCR indicated that ciRs-126 expression was downregulated while miR-21 expression was upregulated in PCOS samples and insulin-induced granulosa cells as compared with non-PCOS samples and non-insulin-induced granulosa cells. Furthermore, ectopic overexpression of ciRS-126 was associated with a reduction in proliferation and increased apoptosis in insulin-treated granulosa cells. Meanwhile, bioinformatic prediction and the results of the dual-luciferase reporter assay indicated the presence of consecutive binding in the ciRS-126-miR-21-programmed cell death protein 4 (PDCD4) axis. Moreover, overexpression of miR-21 blocked ciRS-126 repression of proliferation and triggered the death of insulin-induced granulosa cells. Excessive PDCD4 expression counteracted the influence of miR-21 on cell death and proliferation. The data indicated that PDCD4 played a regulatory role in ROS generation, which is reportedly involved in apoptosis. Therefore, ciRS-126 reduction in PCOS granulosa cells targeted the miR-21-PDCD4 axis to reduce proliferation and promote apoptosis. CiRS-126 shows potential as a promising predictor of clinical outcome as well as a therapeutic target in PCOS.

中文翻译：

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CiRS-126通过靶向miR-21-PDCD4-ROS轴抑制多囊卵巢综合征模型中卵巢颗粒细胞的增殖

多囊卵巢综合征 (PCOS) 被认为是影响育龄妇女的最普遍的内分泌疾病之一。CiRS-126 是一种创新的环状 microRNA，此前已被证明是一种很有前途的 miR-21 海绵。然而，需要正确理解 ciRS-126 对 PCOS 的影响。最初在 18 名 PCOS 女性和 9 名非 PCOS 女性的卵巢皮质样本中评估了环状 RNA (CiRS) 谱。从小鼠中分离的胰岛素诱导的卵巢颗粒细胞用于功能研究。CiRS 微阵列分析和实时定量 PCR 表明，与非 PCOS 样品和非胰岛素诱导的颗粒细胞相比，PCOS 样品和胰岛素诱导的颗粒细胞中 ciRs-126 表达下调而 miR-21 表达上调。此外，ciRS-126 的异位过表达与胰岛素处理的颗粒细胞增殖减少和细胞凋亡增加有关。同时，生物信息学预测和双荧光素酶报告基因检测的结果表明在 ciRS-126-miR-21 程序化的细胞死亡蛋白 4 (PDCD4) 轴中存在连续结合。此外，miR-21 的过表达阻断了 ciRS-126 对增殖的抑制并引发了胰岛素诱导的颗粒细胞的死亡。过度的PDCD4表达抵消了miR-21对细胞死亡和增殖的影响。数据表明 PDCD4 在 ROS 生成中发挥调节作用，据报道其与细胞凋亡有关。因此，PCOS 颗粒细胞中 ciRS-126 的减少靶向 miR-21-PDCD4 轴以减少增殖并促进细胞凋亡。