Center for Reproduction and Genetics, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, No. 26 Daoqian Street, Gusu District, Suzhou, 215002, Jiangsu, China.
Zhenjiang College, Zhenjiang, 212000, Jiangsu, China.
Cell Tissue Res. 2020 Jul;381(1):189-201. doi: 10.1007/s00441-020-03187-9. Epub 2020 May 29.
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.
多囊卵巢综合征（PCOS）被认为是最常见的影响育龄妇女的内分泌疾病之一。CiRS-126 是一种创新性的环状 microRNA，之前已被证明是 miR-21 的一种有前途的海绵体。然而，需要正确理解 ciRS-126 对 PCOS 的影响。
首先在 18 名患有 PCOS 的女性和 9 名无 PCOS 的女性的卵巢皮质样本中评估了环状 RNA（CiRS）图谱。从老鼠中分离的胰岛素诱导的卵巢颗粒细胞用于功能研究。CiRS 微阵列分析和定量实时 PCR 表明，与非 PCOS 样本和非胰岛素诱导的颗粒细胞相比，PCOS 样本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，外源性过表达 ciRS-126 与胰岛素处理的颗粒细胞增殖减少和凋亡增加有关。同时，生物信息学预测和双荧光素酶报告基因检测结果表明，在 ciRS-126-miR-21-程序性细胞死亡蛋白 4（PDCD4）轴中存在连续结合。此外，miR-21 的过表达阻断了 ciRS-126 对增殖的抑制作用，并触发了胰岛素诱导的颗粒细胞死亡。过度表达的 PDCD4 抵消了 miR-21 对细胞死亡和增殖的影响。数据表明，PDCD4 在 ROS 产生中发挥调节作用，ROS 据称参与细胞凋亡。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凋亡。CiRS-126 有望成为 PCOS 临床结果的有前途的预测因子和治疗靶点。
