Aberration in microRNA expression or DNA methylation is a causal factor for polycystic ovarian syndrome. However, the epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. We conducted a novel integrated analysis of RNA-seq, miRNA-seq, and methylated DNA-binding domain sequencing on ovarian granulosa cells to reveal the epigenetic interactions involved in the pathogenesis of PCOS. We identified 830 genes and 30 miRNAs that were expressed differently in PCOS, and seven miRNAs negatively regulated target mRNA expression. 130 miRNAs’ promoters were significantly differently methylated, while 13 were associated with miRNA expression. Furthermore, the hypermethylation of miR-429, miR-141-3p, and miR-126-3p′ promoter was found related to miRNA expression suppression and therefore their corresponding genes upregulation, including XIAP, BRD3, MAPK14, and SLC7A5. Our findings provide a novel insight in PCOS. The consequential reversal of genes silencing may participate in PCOS pathogenesis and served as potential molecular targets for PCOS.

microRNA 表达或 DNA 甲基化的异常是多囊卵巢综合征的一个致病因素。然而，miRNA 和 DNA 甲基化之间的表观遗传相互作用在 PCOS 中仍未得到探索。我们对卵巢颗粒细胞的 RNA-seq、miRNA-seq 和甲基化 DNA 结合域测序进行了新的综合分析，以揭示 PCOS 发病机制中涉及的表观遗传相互作用。我们确定了在 PCOS 中表达不同的 830 个基因和 30 个 miRNA，其中 7 个 miRNA 负向调节靶 mRNA 的表达。130 个 miRNA 的启动子被显着不同的甲基化，而 13 个与 miRNA 表达相关。此外，发现 miR-429、miR-141-3p 和 miR-126-3p' 启动子的高甲基化与 miRNA 表达抑制相关，因此它们相应的基因上调，XIAP、BRD3、MAPK14和SLC7A5。我们的研究结果为 PCOS 提供了新的见解。随之而来的基因沉默逆转可能参与 PCOS 发病机制，并作为 PCOS 的潜在分子靶点。