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通过蛋白质-蛋白质相互作用网络分析探讨多囊卵巢综合征的潜在分子机制。

Explore the potential molecular mechanism of polycystic ovarian syndrome by protein-protein interaction network analysis.

机构信息

Reproductive Medicine Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350001, PR China.

Reproductive Medicine Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350001, PR China.

出版信息

Taiwan J Obstet Gynecol. 2021 Sep;60(5):807-815. doi: 10.1016/j.tjog.2021.07.005.

DOI:10.1016/j.tjog.2021.07.005
PMID:34507653
Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders prevailing in reproductive age women, present in 3-15% population of women worldwide. Although there are many studies on PCOS, its underlying mechanism remains to be determined. The present study was to construct protein-protein interaction networks based on the potential disease-causing genes for PCOS and characterize the underlying molecular mechanisms of PCOS using the networks. PCOS-associated genes were extracted from DisGeNet and the protein-protein interaction networks (PPIN) of PCOS were constructed using the String Database. Then we utilized MCODE algorithm to analyse the hub-gene modules from the PPIN. Finally, the major biological functions and signaling pathways involved in the hub modules were explored by functional enrichment analysis. A total of 522 candidate genes associated to PCOS were extracted from DisGeNET database. The PPIN constructed using the genes we have collected above included 488 genes and 2767 interaction relationships. Moreover, seven major gene modules were obtained after analyzing the PPIN with the use of MCODE plug-in. The major modules generated were enriched in certain biological functions such as cancer and cell proliferation and apoptosis, regulation of lipid and glucose metabolism, cell cycle and so on. The integrated analysis performed in the current study revealed that these hub modules and their related genes are closely associated to the pathogenesis of PCOS, which may probably provide novel insights for the treatment of PCOS and the study of its latent pathogenic mechanism. The relationship between several of the key genes including ALB, TOP2A, PTGER3, NPB and BRD2 in the modules and PCOS has not been investigated previously and it remains to be verified by further research of large sample, multi-center and multi-ethnic.

摘要

多囊卵巢综合征(PCOS)是生殖年龄妇女中最常见的内分泌疾病之一,全球范围内有 3-15%的妇女患有该病。尽管已经有许多关于 PCOS 的研究,但它的潜在发病机制仍有待确定。本研究旨在基于 PCOS 的潜在致病基因构建蛋白质-蛋白质相互作用网络,并利用这些网络来表征 PCOS 的潜在分子机制。从 DisGeNet 中提取 PCOS 相关基因,并使用 String Database 构建 PCOS 的蛋白质-蛋白质相互作用网络(PPIN)。然后,我们利用 MCODE 算法从 PPIN 中分析枢纽基因模块。最后,通过功能富集分析探讨枢纽模块中涉及的主要生物学功能和信号通路。从 DisGeNET 数据库中提取了 522 个与 PCOS 相关的候选基因。使用我们收集的基因构建的 PPIN 包含 488 个基因和 2767 个相互作用关系。此外,使用 MCODE 插件分析 PPIN 后获得了 7 个主要基因模块。生成的主要模块在某些生物学功能中得到了富集,如癌症和细胞增殖与凋亡、脂质和葡萄糖代谢的调节、细胞周期等。本研究的综合分析表明,这些枢纽模块及其相关基因与 PCOS 的发病机制密切相关,这可能为 PCOS 的治疗和潜在发病机制的研究提供新的思路。模块中包括 ALB、TOP2A、PTGER3、NPB 和 BRD2 在内的几个关键基因与 PCOS 之间的关系以前没有被研究过,需要通过进一步的大样本、多中心和多民族研究来验证。

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