Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of polycystic ovarian syndrome.

IF 1.7 4区医学 Q2 MEDICINE, GENERAL & INTERNAL Irish Journal of Medical Science Pub Date : 2024-12-01 Epub Date: 2024-09-06 DOI:10.1007/s11845-024-03795-2

Prajna Bhandary, Dhananjay B Alagundagi, Prasanna Kumar Shetty, Prakash Patil

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Abstract

Background: Polycystic ovarian syndrome (PCOS), a gynae-endocrine disorder, has a relatively high risk of differential expression of miRNA (DE-miRNA) in the disease progression.

Aims: To identify the DE-miRNA in the progression of PCOS in the ovarian cumulus cells.

Methods: The microarray dataset GSE72274 was analysed for PCOS-associated DE-miRNAs. miRNet identifies the target genes. Protein-protein interaction (PPI) network was constructed and hub genes were analysed by topology and module analysis. Transcription factors (TFs) and protein kinases (PKs) regulating the hub genes were identified using X2K tool. Biological functions were analysed using DAVID software. Finally, the DGIdb drug-gene interaction tool identifies the candidate medications.

Results: A total of 1577 DE-miRNAs linked to PCOS were identified, with 13 meeting the specified criteria. Subsequently, its 2053 target genes were retrieved through miRNet. Topology and module analysis identified the hub genes VEGFA, SOX2, KRAS, AKT1, and SMAD4 that are implicated in ovarian regulation. Notably, the study highlighted the significant role of the wnt signalling pathway, which is involved in ovarian function, specifically in follicle development, corpus luteum formation, and steroid production. Additionally, six TFs and PKs were identified as important regulators of these hub genes, and the potential medication interactions identified 11 medicines for VEGFA, KRAS, AKT1, and SMAD4 genes, while no suitable drug for SOX2 was identified.

Conclusion: Identified, hub genes are known to associate with the regulation of ovarian function such as oocyte development, and steroid synthesis via the wnt signalling pathway.

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鉴定导致多囊卵巢综合征发病机制的潜在 miRNA-mRNA 调控网络。

背景：多囊卵巢综合征（PCOS）是一种妇科内分泌疾病，在疾病进展过程中，miRNA（DE-miRNA）差异表达的风险相对较高：方法：对微阵列数据集 GSE72274 进行分析，寻找与 PCOS 相关的 DE-miRNA。构建了蛋白-蛋白相互作用（PPI）网络，并通过拓扑和模块分析法分析了枢纽基因。利用 X2K 工具鉴定了调控枢纽基因的转录因子（TFs）和蛋白激酶（PKs）。使用 DAVID 软件分析了生物功能。最后，利用 DGIdb 药物基因相互作用工具确定候选药物：结果：共鉴定出 1577 个与多囊卵巢综合征相关的 DE-miRNA，其中 13 个符合特定标准。随后，通过 miRNet 检索到其 2053 个靶基因。拓扑和模块分析确定了与卵巢调控有关的枢纽基因 VEGFA、SOX2、KRAS、AKT1 和 SMAD4。值得注意的是，该研究强调了 wnt 信号通路的重要作用，它参与卵巢功能，特别是卵泡发育、黄体形成和类固醇生成。此外，还发现了六种TFs和PKs是这些枢纽基因的重要调控因子，潜在的药物相互作用发现了11种治疗VEGFA、KRAS、AKT1和SMAD4基因的药物，但没有发现适合治疗SOX2的药物：结论：已发现的枢纽基因与卵巢功能的调控有关，如卵母细胞发育和通过 wnt 信号通路的类固醇合成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Irish Journal of Medical Science 医学-医学：内科

CiteScore

3.70

自引率

4.80%

发文量

357

审稿时长

4-8 weeks

期刊介绍： The Irish Journal of Medical Science is the official organ of the Royal Academy of Medicine in Ireland. Established in 1832, this quarterly journal is a contribution to medical science and an ideal forum for the younger medical/scientific professional to enter world literature and an ideal launching platform now, as in the past, for many a young research worker. The primary role of both the Academy and IJMS is that of providing a forum for the exchange of scientific information and to promote academic discussion, so essential to scientific progress.