CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179
CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179
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DOI：
10.1016/j.repbio.2022.100637
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发表时间：
2022-03-25
影响因子：
2.1
通讯作者：
Xuan, Fei-Lan
中科院分区：
文献类型：
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作者：
Chen, Ai-Xue;Jin, Rui-Ying;Xuan, Fei-Lan
越来越多的证据表明，环状RNA（CircRNA）在人类疾病中起着重要作用，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，它在PCOS中的作用尚未被探索。在这项研究中，通过qRT-PCR分析检测了卵巢颗粒细胞（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印迹测定来检查OGC系COV 434和KGN中的circ_0043533的敲低、胰岛素触发的OGC的细胞活力、增殖、凋亡和周期相关标志物。通过生物信息学、双荧光素酶测定和RNA免疫沉淀来检查circ_0043533与miR 1179之间的相互作用。此外，还评估了miR-1179抑制剂对circ_0043533敲低的OGC系中细胞活力和细胞凋亡的影响。与IOSE 80细胞相比，OGC和胰岛素处理的OGC表现出更高的circ_0043533水平。此外，敲低circ_0043533分别显著抑制胰岛素处理的COV 434和KGN细胞的细胞活力和增殖，并促进细胞凋亡。同时，circ_0043533基因敲低可下调Bcl-2、CDK 2和Cyclin D1的表达，上调Bax的表达。此外，我们证明了circ_0043533作为海绵吸收miR-1179。有趣的是，miR 1179抑制显著减弱了胰岛素处理的COV 434和KGN细胞中circ_0043533沉默对细胞增殖和凋亡的影响。综上所述，该研究揭示了circ_0043533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将作为PCOS的新的治疗靶点。
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 miR1179 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, miR1179 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.