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分析妊娠期糖尿病患者胎盘组织中的关键基因及其功能。

Analysis of key genes and their functions in placental tissue of patients with gestational diabetes mellitus.

机构信息

Department of Gynecology, Jinan Central Hospital, Jinan City, 250013, Shandong Province, China.

Department of Obstetrics, Jinan Central Hospital, No. 105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China.

出版信息

Reprod Biol Endocrinol. 2019 Nov 29;17(1):104. doi: 10.1186/s12958-019-0546-z.

Abstract

BACKGROUND

This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM).

METHODS

The GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA-transcription factor (TF)-DEG regulatory network was analyzed.

RESULTS

In total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted.

CONCLUSIONS

Four candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.

摘要

背景

本研究旨在筛选与妊娠期糖尿病(GDM)相关的潜在关键基因和通路。

方法

本研究使用的 GSE70493 数据集来自基因表达综合数据库。鉴定出 GDM 患者胎盘组织与对照组织样本中差异表达的基因(DEGs),并提交给蛋白质-蛋白质相互作用(PPI)网络分析和子网络模块挖掘。随后对 PPI 网络和子网进行功能富集分析。最后,分析整合的 miRNA-转录因子(TF)-DEG 调控网络。

结果

共鉴定出 238 个 DEGs,其中 162 个上调,76 个下调。通过 PPI 网络构建,获得了 108 个节点和 278 个基因对,从中筛选出趋化因子(C-X-C 基序)配体 9(CXCL9)、CXCL10、蛋白酪氨酸磷酸酶,受体 C 型(PTPRC)和人类白细胞抗原(HLA)作为枢纽基因。此外,与免疫相关途径和免疫反应相关的基因在 GDM 过程中明显富集。最后,预测了针对 DEGs 的 miRNA 和 TF。

结论

四个候选基因(即 CXCL9、CXCL10、PTPRC 和 HLA)与 GDM 密切相关。miR-223-3p、miR-520 和硫氧还蛋白结合蛋白可能在该疾病的发病机制中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d55e/6884804/8f792951a71c/12958_2019_546_Fig1_HTML.jpg

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