Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8
Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8
复制标题
PCOS 患者卵丘细胞中改变的 microRNA 和 mRNA 的鉴定：miRNA-509-3p 通过靶向 MAP3K8 促进雌二醇分泌
DOI：
10.1530/rep-16-0071
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发表时间：
2016-06-01
期刊：
影响因子：
3.8
通讯作者：
Yan, Wei
中科院分区：
文献类型：
--
作者：
Huang, Xin;Liu, Chang;Yan, Wei
多囊卵巢综合征（PCOS）是一种常见的内分泌和代谢紊乱的妇女，其特征是多囊卵巢，高雄激素血症和慢性无排卵。虽然PCOS的临床和生化体征通常是异质性的，但卵泡发生异常被认为是PCOS的共同特征。我们的目的是鉴定PCOS患者卵丘细胞中改变的miRNA和mRNA表达谱，以研究其在PCOS病因学和病理生理学中的分子功能。在这项研究中，从5例PCOS患者和5例对照组中分离的卵丘细胞样本的miRNA表达谱通过miRNA微阵列测定。同时，用cDNA微阵列技术对同一卵丘细胞样品中的mRNA表达谱进行了分析。结果表明，在PCOS患者卵丘细胞中，有17个miRNAs和1263个mRNAs的表达存在显著差异。分别从miRNA和mRNA微阵列中鉴定差异表达的miRNA-509- 3 p及其潜在靶基因（MAP 3 K8）。在PCOS卵丘细胞中，miRNA-509- 3 p表达上调，而MAP 3 K8表达下调。通过KGN细胞中的荧光素酶活性测定证实了miRNA-509- 3 p和MAP 3 K8之间的直接相互作用。此外，KGN细胞中的miRNA-509- 3 p模拟物或抑制剂转染试验进一步证实，miRNA-509- 3 p通过抑制MAP 3 K8的表达来改善雌二醇（E-2）分泌。这些结果有助于阐明PCOS无排卵的发病机制，尤其是E_1的调节。
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim is to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to investigate their molecular function in the aetiology and pathophysiology, of PCOS. In this study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by an miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cell samples were also identified by a cDNA microarray. From the microarray data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays respectively. The expression of miRNA-509-3p was up-regulated and MAP3K8 was down-regulated in the PCOS cumulus cells. The direct interaction between miRNA-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miRNA-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miRNA-509-3p improved oestradiol (E-2) secretion by inhibiting the expression of MAP3K8. These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of E, production.