Zhao Jun, Huang Jiayu, Geng Xueying, Chu Weiwei, Li Shang, Chen Zi-Jiang, Du Yanzhi
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Front Genet. 2019 Aug 22;10:772. doi: 10.3389/fgene.2019.00772. eCollection 2019.
Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder with an increasing risk for type 2 diabetes. Insulin resistance is a common feature of women with PCOS, but the underlying molecular mechanism remains unclear. This study aimed to screen critical long non-coding RNAs (lncRNAs) that might play pivotal roles in insulin resistance, which could provide candidate biomarkers and potential therapeutic targets for PCOS. Gene expression profiles of the skeletal muscle in patients with PCOS accompanied by insulin resistance and healthy patients were obtained from the publicly available Gene Expression Omnibus (GEO) database. A global triple network including RNA-binding protein, mRNA, and lncRNAs was constructed based on the data from starBase. Then, we extracted an insulin resistance-associated lncRNA-mRNA network (IRLMN) by integrating the data from starBase and GEO. We also performed a weighted gene co-expression network analysis (WGCNA) on the differentially expressed genes between the women with and without PCOS, to identify hub lncRNAs. Additionally, the findings of key lncRNAs were examined in an independent GEO dataset. The expression level of in ovarian granulosa cells was increased in patients with PCOS compared with that in control women. Levels were also increased in PCOS patients with higher BMI, hyperinsulinemia, and higher HOMA-IR values. As a result, was identified as a hub lncRNA based on IRLMN and WGCNA and was highly expressed in ovarian granulosa cells, skeletal muscle, and subcutaneous and omental adipose tissues of patients with insulin resistance. This study showed the differences between lncRNA and mRNA profiles from healthy women and women with PCOS and insulin resistance. Here, we demonstrated that RP11-151A6.4 might play a vital role in insulin resistance, androgen excess, and adipose dysfunction in patients with PCOS. Further study concerning RP11-151A6.4 could elucidate the underlying mechanisms of insulin resistance.
多囊卵巢综合征（PCOS）是一种常见的代谢和生殖紊乱疾病，患2型糖尿病的风险不断增加。胰岛素抵抗是PCOS女性的一个常见特征，但其潜在的分子机制仍不清楚。本研究旨在筛选可能在胰岛素抵抗中起关键作用的关键长链非编码RNA（lncRNA），这可为PCOS提供候选生物标志物和潜在治疗靶点。伴有胰岛素抵抗的PCOS患者和健康患者骨骼肌的基因表达谱来自公开的基因表达综合数据库（GEO）。基于starBase的数据构建了一个包括RNA结合蛋白、mRNA和lncRNA的全局三重网络。然后，通过整合starBase和GEO的数据，我们提取了一个胰岛素抵抗相关的lncRNA-mRNA网络（IRLMN）。我们还对有PCOS和无PCOS女性之间的差异表达基因进行了加权基因共表达网络分析（WGCNA），以识别枢纽lncRNA。此外，在一个独立的GEO数据集中检查了关键lncRNA的研究结果。与对照女性相比，PCOS患者卵巢颗粒细胞中的表达水平升高。在BMI较高、高胰岛素血症和HOMA-IR值较高的PCOS患者中水平也升高。结果，基于IRLMN和WGCNA将其鉴定为枢纽lncRNA，并且在胰岛素抵抗患者的卵巢颗粒细胞、骨骼肌以及皮下和网膜脂肪组织中高表达。本研究显示了健康女性与患有PCOS和胰岛素抵抗的女性之间lncRNA和mRNA谱的差异。在这里，我们证明了RP11-151A6.4可能在PCOS患者的胰岛素抵抗、雄激素过多和脂肪功能障碍中起重要作用。关于RP11-151A6.4的进一步研究可以阐明胰岛素抵抗的潜在机制。
