Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome
Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome
复制标题
多囊卵巢综合征女性卵泡液中与高雄激素血症相关的 microRNA 和基因的鉴定
DOI：
10.1002/jcb.26531
复制
发表时间：
2018-05-01
影响因子：
4
通讯作者：
Li, Qian
中科院分区：
文献类型：
--
作者：
Xue, Yunping;Lv, Juan;Li, Qian
多囊卵巢综合征（PCOS）是一种常见的生殖内分泌疾病，以高雄激素血症（HA）、慢性无排卵、多囊卵巢、胰岛素抵抗和肥胖为特征。目前，PCOS/HA的发生机制尚未完全阐明，因此，PCOS中HA的发生机制及干预措施是当前研究的热点。最近已经证明，miRNA可作为癌症患者的诊断或预后生物标志物。因此，我们目前专注于研究卵泡液中miRNA表达的改变及其与PCOS中HA的相关性。使用Illumina深度测序技术探索PCOS/HA女性卵泡液和对照组女性卵泡液中的不同miRNA。然后使用靶标预测数据库分析不同表达的miRNAs的靶基因，并使用GO分析和KEGG通路数据库来鉴定差异表达的靶基因的功能和主要的生化和信号通路。263种miRNAs的表达水平在两组女性之间存在显著差异（>2倍上调或<0.5倍下调，P < 0.05）。例如，与对照组相比，PCOS患者中miRNA（200 a-3 p、10 b-3 p、200 b-3 p、29 c-3 p、99 a-3 p和125 a-5 p）的表达水平显著增加，而miR-105 - 3 p的表达水平降低。文献显示上述7种miRNAs与PCOS的HA相关。此外，预测31 770个基因是263个差异表达microRNA的靶基因。GO分析和KEGG通路数据库显示这些靶基因参与PCOS的HA。这些结果表明，PCOS/HA女性与对照组女性相比，卵泡液中存在差异表达的miRNA。使用生物信息学工具阐明了这些microRNA的潜在作用，并发现它们参与调节PCOS的不同途径、生物学功能和细胞组分。本研究结果可能揭示PCOS/HA的新机制，并提出潜在的治疗靶点。
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which is characterized by hyperandrogenism (HA), chronic anovulation, polycystic ovaries, insulin resistance, and obesity. At present, the mechanism by which PCOS/HA occurs has not been fully elucidated, thus, the mechanisms behind and interventions for HA in PCOS are current hot topics in research. MiRNAs have recently been shown to serve as diagnostic or prognostic biomarkers in patients with cancer. Thus, we are currently focused on studying the altered expression of miRNAs in follicular fluid and their correlation with HA in PCOS. Illumina deep sequencing technology was used to explore different miRNAs in the follicular fluid of women with PCOS/HA and in the follicular fluid of women in a control group. Target prediction databases were then used to analyse the target genes of different expressed miRNAs, and GO analysis and the KEGG pathway database were used to identify the functions and the main biochemical and signalling pathways of differentially expressed target genes. The expression levels of 263 miRNAs were significantly different (>2‐fold up‐regulated or <0.5‐fold down‐regulated, P < 0.05) between the two groups of women. For example, the expression levels of miRNA (200a‐3p, 10b‐3p, 200b‐3p, 29c‐3p, 99a‐3p, and 125a‐5p) were significantly increased, while there was a decreased expression of miR‐105‐3p in PCOS patients with respect to the control. Literature has shown that the above seven miRNAs were associated with HA in PCOS. Furthermore, 31 770 genes were predicted to be targets of the 263 differentially expressed microRNAs. GO analysis and the KEGG pathway database showed involvement of these target genes in HA in PCOS. These results suggest the presence of differentially expressed miRNAs in the follicular fluid of women with PCOS/HA versus women in the control group. The potential role of these microRNAs was elucidated using bioinformatics tools and was found to be involved in the regulation of different pathways, biological functions, and cellular components underlying PCOS. The results of this research may reveal new mechanisms of PCOS/HA and suggest potential treatment targets.