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基于生物信息学分析鉴定 2 型糖尿病与多囊卵巢综合征的关键基因及分子通路

Identification of key genes and molecular pathways in type 2 diabetes mellitus and polycystic ovary syndrome via bioinformatics analyses.

机构信息

Department of Pediatrics, Shandong Second Provincial General Hospital, Jinan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2023 Apr;27(8):3255-3269. doi: 10.26355/eurrev_202304_32097.

DOI:10.26355/eurrev_202304_32097
PMID:37140276
Abstract

OBJECTIVE

Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) are highly prevalent endocrine system diseases. However, studies on the molecular mechanisms of T2DM and PCOS at the transcriptomic level are still few. Thus, we aimed to reveal the potential common genetic and molecular pathways between T2DM and PCOS via bioinformatics analyses.

MATERIALS AND METHODS

We downloaded the GSE10946 and GSE18732 datasets for T2DM and PCOS, respectively, from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database. These datasets were subjected to integrated differential and weighted gene co-expression network analyses (WGCNA) to screen common genes. Thereafter, functional enrichment and disease gene association analyses were performed, transcription factor (TF)-gene and TF-miRNA-gene regulatory networks were constructed, and finally, the relevant target drugs were identified.

RESULTS

We identified common genes (BIRC3, DEPTOR, TNNL3, ADRA2A) in T2DM and PCOS. Pathway enrichment analysis depicted that the common genes were enriched in smooth muscle contraction, channel inhibitor activity, apoptosis, and tumor necrosis factor (TNF) signaling pathways. TFs such as SP7, KLF8, HCFC1, IRF1, and MLLT1 played key roles in TF regulatory networks. Orlistat was indicated to be an important gene-targeting drug.

CONCLUSIONS

This study is the first study to explore four diagnostic biomarkers and gene regulatory networks for T2DM and PCOS. The findings of our study provide novel insights into the diagnosis and treatment of T2DM and PCOS.

摘要

目的

2 型糖尿病(T2DM)和多囊卵巢综合征(PCOS)是两种常见的内分泌系统疾病。然而,基于转录组水平研究 T2DM 和 PCOS 分子机制的相关工作仍然较少。因此,我们旨在通过生物信息学分析揭示 T2DM 和 PCOS 之间潜在的共同遗传和分子途径。

材料和方法

我们从美国国立生物技术信息中心基因表达综合数据库(GEO)下载了 GSE10946 和 GSE18732 数据集,分别用于 T2DM 和 PCOS。我们对这些数据集进行了综合差异和加权基因共表达网络分析(WGCNA),以筛选共同基因。然后,我们进行了功能富集和疾病基因关联分析,构建了转录因子(TF)-基因和 TF-miRNA-基因调控网络,并最终确定了相关的靶标药物。

结果

我们在 T2DM 和 PCOS 中鉴定出共同基因(BIRC3、DEPTOR、TNNL3、ADRA2A)。通路富集分析显示,共同基因富集在平滑肌收缩、通道抑制剂活性、细胞凋亡和肿瘤坏死因子(TNF)信号通路中。SP7、KLF8、HCFC1、IRF1 和 MLLT1 等 TF 在 TF 调控网络中发挥关键作用。奥利司他被认为是一种重要的基因靶向药物。

结论

本研究首次探索了 T2DM 和 PCOS 的四个诊断生物标志物和基因调控网络。我们的研究结果为 T2DM 和 PCOS 的诊断和治疗提供了新的见解。

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