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miR-222 通过靶向 p27 Kip1 促进多囊卵巢综合征的进展。

MiR-222 promotes the progression of polycystic ovary syndrome by targeting p27 Kip1.

机构信息

Department of Reproductive Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, 362000, PR China.

Department of Reproductive Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, 362000, PR China.

出版信息

Pathol Res Pract. 2019 May;215(5):918-923. doi: 10.1016/j.prp.2019.01.038. Epub 2019 Jan 28.

DOI:10.1016/j.prp.2019.01.038
PMID:30718101
Abstract

Polycystic ovary syndrome (PCOS) is one of the most complex and common reproductive and endocrinologic disorders in the child-bearing age of women. Recently, miR-222 were reported to be associated with the etiology of PCOS. However, the function of miR-222 during the pathogenesis of PCOS remains unclear. In the present study, we aimed to investigate the role of miR-222 in PCOS. Firstly, miR-222 expression was examined by quantitative real-time PCR (qRT-PCR) in PCOS. The effects of miR-222 on proliferation, apoptosis and cell cycle in KGN cells were analyzed by CCK-8 assay and flow cytometry analysis, respectively. In addition, bioinformatics analysis was used to predict the target genes of miR-222, and dual-luciferase reporter assay was applied to verified the interaction between miR-222 and p27 Kip1 in KGN cells. Moreover, the expressions of p27 Kip1 in KGN cells treated with miR-222 mimics or miR-222 inhibitor were evaluated by qRT-PCR and western blot assays. The results showed that the expression of miR-222 was remarkably upregulated in PCOS tissues compared with corresponding normal tissues. In the gain-of-function and loss-of-function assays, we revealed that miR-222 mimics significantly promoted cell proliferation, while miR-222 inhibitor induced cell apoptosis and cell cycle arrested. Furthermore, p27 Kip1 was identified as a target gene of miR-222, and could be negatively regulated by miR-222 mimics in KGN cells. In conclusion, our findings suggested that miR-222 may promote the progression of PCOS by targeting p27 Kip1.

摘要

多囊卵巢综合征(PCOS)是育龄妇女最复杂和常见的生殖和内分泌疾病之一。最近,有研究报道 miR-222 与 PCOS 的病因有关。然而,miR-222 在 PCOS 发病机制中的作用尚不清楚。在本研究中,我们旨在研究 miR-222 在 PCOS 中的作用。首先,通过定量实时 PCR(qRT-PCR)检测 PCOS 中 miR-222 的表达。通过 CCK-8 检测和流式细胞术分析分别检测 miR-222 对 KGN 细胞增殖、凋亡和细胞周期的影响。此外,利用生物信息学分析预测 miR-222 的靶基因,并应用双荧光素酶报告基因检测验证 miR-222 与 KGN 细胞中 p27 Kip1 的相互作用。此外,通过 qRT-PCR 和 Western blot 检测评估 miR-222 模拟物或 miR-222 抑制剂处理的 KGN 细胞中 p27 Kip1 的表达。结果表明,与相应的正常组织相比,PCOS 组织中 miR-222 的表达明显上调。在功能获得和功能丧失实验中,我们发现 miR-222 模拟物显著促进细胞增殖,而 miR-222 抑制剂诱导细胞凋亡和细胞周期停滞。此外,p27 Kip1 被鉴定为 miR-222 的靶基因,并且可以被 miR-222 模拟物在 KGN 细胞中负调控。综上所述,我们的研究结果表明,miR-222 可能通过靶向 p27 Kip1 促进 PCOS 的进展。

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