Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, PR China.
Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, PR China.
Gene. 2020 Jun 20;744:144591. doi: 10.1016/j.gene.2020.144591. Epub 2020 Mar 24.
Polycystic ovary syndrome (PCOS) is a kind of endocrine disease among women across the global. Recently, many researches have reported circular RNAs can act as significant molecular biomarkers for diseases, especially in tumors. Several Circular RNAs are reported to be aberrantly expressed in PCOS patients. Here, we investigated the biological effects of hsa_circ_0118530 on human granulosa cells, KGN. We observed that hsa_circ_0118530 was greatly elevated in PCOS patients and granulosa cells (including KGN and COV434 cells) compared to normal IOSE80 cells. hsa_circ_0118530 siRNA was transfected into KGN cells. We found that KGN cell viability was repressed, cell apoptosis was induced while cell migration was greatly inhibited. TGF-β1 was utilized to induce EMT process. As shown, loss of hsa_circ_0118530 significantly enhanced E-cadherin mRNA and protein levels while depressed N-cadherin expression. Furthermore, we indicated that decrease of hsa_circ_0118530 was able to inhibit ROS accumulation, MDA levels while induced SOD activity. Next, it was demonstrated that releases of inflammatory cytokine were suppressed by hsa_circ_0118530 down-regulation. Additionally, miR-136 was predicted and confirmed as the target of hsa_circ_0118530. For another, the functions of hsa_circ_0118530 on KGN cell progression, oxidative stress and inflammation releases were obviously reversed by miR-136 suppression. In conclusion, knockdown of hsa_circ_0118530 repressed PCOS progression via sponging miR-136.
多囊卵巢综合征(PCOS)是一种全球女性内分泌疾病。最近,许多研究报告称,环状 RNA 可以作为疾病的重要分子生物标志物,尤其是在肿瘤中。有报道称,几种环状 RNA 在 PCOS 患者中表达异常。在这里,我们研究了 hsa_circ_0118530 对人颗粒细胞(KGN)的生物学效应。我们观察到,与正常 IOSE80 细胞相比,PCOS 患者和颗粒细胞(包括 KGN 和 COV434 细胞)中 hsa_circ_0118530 的表达水平显著升高。将 hsa_circ_0118530 siRNA 转染到 KGN 细胞中。我们发现 KGN 细胞活力受到抑制,细胞凋亡被诱导,而细胞迁移则受到很大抑制。利用 TGF-β1 诱导 EMT 过程。结果表明,hsa_circ_0118530 的缺失显著增强了 E-钙黏蛋白 mRNA 和蛋白水平,而抑制了 N-钙黏蛋白的表达。此外,我们表明,hsa_circ_0118530 的减少能够抑制 ROS 积累、MDA 水平,同时诱导 SOD 活性。接下来,研究表明 hsa_circ_0118530 的下调能够抑制炎症细胞因子的释放。此外,miR-136 被预测并证实为 hsa_circ_0118530 的靶标。另外,hsa_circ_0118530 对 KGN 细胞增殖、氧化应激和炎症释放的作用明显被 miR-136 抑制所逆转。总之,hsa_circ_0118530 的敲低通过海绵吸附 miR-136 抑制了 PCOS 的进展。