Qin Yulan, Wang Yuhuan, Zhao Hui, Yang Zhaoxia, Kang Yani
School of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai, China.
Ann Transl Med. 2021 Sep;9(18):1405. doi: 10.21037/atm-21-1288.
Polycystic ovary syndrome (PCOS) is a common multifactorial metabolic and endocrine disorder in women of reproductive age. Increasingly, evidence indicates that the microRNA (miRNA)-mRNA axis contributes to the development of PCOS.
To investigate the molecular mechanisms through which miRNA-mRNA expression affects hyperandrogenism, ovarian tissue samples from prenatally androgenized (PNA) mice were subjected to miRNA-seq and RNA-seq analysis. Analyses were performed to identify differentially expressed microRNAs (DEmiRs) and differentially expressed genes (DEGs). In combination with our previous data obtained from clinical samples, we have performed an integrated miRNA-mRNA analysis of PNA mice and granulosa cells (GCs) from patients with PCOS. The changes in expression were validated by RT-qPCR in more mouse models and clinical samples.
In total, 3,432 genes and 16 miRNAs were differentially expressed in PNA mice compared with the control mice. We investigated the regulation pattern of miRNAs-mRNAs and observed a total of 12 miRNA-mRNA pairs involved in negative regulation. Functional analysis concentrated on insulin resistance, the T cell receptor signaling pathway, and other inflammation-related pathways. Verification of these results by RT-qPCR showed that the expression of miR-106-5p and miR-155-5p in clinical GCs was consistent with that in PNA mice. After predicting the target genes of miR-106-5p and miR-155-5p and performing negative regulation analysis, six target genes were obtained in GCs. The integration analysis showed that the network of miR-106-5p/miR-155-5p targets was mostly concentrated in pathway related to insulin resistance and inflammation. In addition, the upregulation of the inflammatory genes / and / was validated in the PNA mice and GCs from patients compared with the appropriate control sample. The experiments showed that the regulatory relationship observed may be related to the direct stimulation of DHT.
Our results showed that the miRNA-mRNA regulatory network in PCOS was associated with markers of insulin sensitivity and inflammation. Our study provides a new genetic basis and novel insight regarding the pathogenesis of PCOS.
多囊卵巢综合征（PCOS）是育龄期女性常见的多因素代谢和内分泌紊乱疾病。越来越多的证据表明，微小RNA（miRNA）-信使核糖核酸（mRNA）轴参与了PCOS的发生发展。
为了研究miRNA-mRNA表达影响高雄激素血症的分子机制，对产前雄激素化（PNA）小鼠的卵巢组织样本进行了miRNA测序和RNA测序分析。进行分析以鉴定差异表达的微小RNA（DEmiRs）和差异表达基因（DEGs）。结合我们先前从临床样本中获得的数据，我们对PNA小鼠和PCOS患者的颗粒细胞（GCs）进行了综合的miRNA-mRNA分析。通过逆转录定量聚合酶链反应（RT-qPCR）在更多的小鼠模型和临床样本中验证了表达变化。
与对照小鼠相比，PNA小鼠中共有3432个基因和16个miRNA差异表达。我们研究了miRNA-mRNA的调控模式，共观察到12对参与负调控的miRNA-mRNA。功能分析集中在胰岛素抵抗、T细胞受体信号通路和其他炎症相关通路上。通过RT-qPCR对这些结果进行验证，结果显示临床GCs中miR-106-5p和miR-155-5p的表达与PNA小鼠中的表达一致。在预测miR-106-5p和miR-155-5p的靶基因并进行负调控分析后，在GCs中获得了6个靶基因。整合分析表明，miR-106-5p/miR-155-5p靶标网络主要集中在与胰岛素抵抗和炎症相关的通路上。此外，与相应对照样本相比，在PNA小鼠和患者的GCs中验证了炎症基因/和/的上调。实验表明，观察到的调控关系可能与双氢睾酮（DHT）的直接刺激有关。
我们的结果表明，PCOS中的miRNA-mRNA调控网络与胰岛素敏感性和炎症标志物相关。我们的研究为PCOS的发病机制提供了新的遗传基础和新见解。
