WHO Collaborating Centre, Division of Neonatology, Obstetrics, Gynecology, and Reproductive Health, Department of Women's and Children's Health, Karolinska University Hospital, Karolinska Institutet, SE 17176 Stockholm, Sweden.
Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Centre, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland.
Biomolecules. 2024 Nov 3;14(11):1400. doi: 10.3390/biom14111400.
(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n = 15) and non-endometriosis controls (n = 17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n = 10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation-associated pathways. Further ex vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were upregulated in endometrioma. Overexpression of these two miRNAs in vitro inhibited cell migration, and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.
（1）背景：子宫内膜异位症是一种常见的妇科疾病，全球约有 10%的育龄妇女受其影响。miRNA 可能在子宫内膜异位症中发挥作用，但具体功能尚不清楚。本研究旨在鉴定子宫内膜异位症中差异表达的 miRNA，并研究其在疾病中的作用。（2）方法：收集子宫内膜异位症患者（n=15）和非子宫内膜异位症对照组（n=17）的子宫内膜组织。通过小 RNA-seq 鉴定失调的 miRNA，通过靶基因预测和通路分析探索其生物学意义。使用 qRT-PCR 在配对的异位子宫内膜瘤和在位子宫内膜（n=10）中检测选定的 miRNA。通过功能测定在体外进一步研究它们在细胞迁移和增殖中的作用。为了鉴定潜在的靶基因，我们对转染细胞和子宫内膜瘤队列进行了 mRNA 测序。（3）结果：与无子宫内膜异位症的女性相比，我们在子宫内膜异位症患者的在位子宫内膜中发现了 14 个失调的 miRNA。通路分析表明，这些 miRNA 与细胞迁移和增殖相关的途径富集。对 miR-193b-5p 和 miR-374b-5p 的进一步离体研究表明，这两种 miRNA 在子宫内膜瘤中均上调。这两种 miRNA 的过表达在体外抑制了细胞迁移，mRNA 测序揭示了几个受这些 miRNA 靶向调控的迁移相关基因。（4）结论：我们的研究发现了两种关键的子宫内膜 miRNA，它们可能通过调节细胞迁移参与子宫内膜异位症的发病机制。
