Department of Gynecology, Changxing People's Hospital of Chongming District, Shanghai, China.
Department of Gynecology, Jiaojiang Maternal and Child Health Hospital, Taizhou City, Zhejiang, China.
Reprod Biol. 2022 Jun;22(2):100637. doi: 10.1016/j.repbio.2022.100637. Epub 2022 Mar 25.
Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.
越来越多的证据表明，环状 RNA（circRNAs）在人类疾病中发挥着重要作用，包括多囊卵巢综合征（PCOS）。最近，一种新的 circRNA circ_0043533 被提出参与 PCOS 的进展。然而，其在 PCOS 中的作用尚未得到探索。在这项研究中，通过 qRT-PCR 分析检测卵巢颗粒细胞（OGC）中 circ_0043533 和 miR-1179 的表达水平。此外，分别通过 CCK-8、EdU 染色、流式细胞术和 Western blot 检测 circ_0043533 在 OGC 系 COV434 和 KGN 中的敲低后，胰岛素诱导的 OGC 细胞的活力、增殖、凋亡和周期相关标志物。通过生物信息学、双荧光素酶报告基因检测和 RNA 免疫沉淀检测 circ_0043533 与 miR-1179 的相互作用。此外，还评估了 miR-1179 抑制剂对具有 circ_0043533 敲低的 OGC 系细胞活力和凋亡的影响。与 IOSE80 细胞相比，OGC 和胰岛素处理的 OGC 显示出更高的 circ_0043533 水平。此外，circ_0043533 的敲低显着抑制了胰岛素处理的 COV434 和 KGN 细胞的活力和增殖，并分别促进了细胞凋亡。同时，circ_0043533 的敲低可以下调 Bcl-2、CDK2 和 Cyclin D1 的表达，并上调 Bax 水平。此外，我们证明 circ_0043533 作为 miR-1179 的海绵起作用。有趣的是，miR-1179 抑制显着减弱了 circ_0043533 沉默对胰岛素处理的 COV434 和 KGN 细胞增殖和凋亡的影响。总之，这项研究表明，circ_0043533 的敲低通过靶向 miR-1179 抑制 PCOS 的恶性进展。我们的数据表明，circ_0043533 可以作为 PCOS 的一种新的治疗靶点。
