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Published online: 2023-03-10
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A preliminary integrated analysis of miRNA-mRNA expression profiles reveals a role of miR-146a-3p/TRAF6 in plasma from gestational diabetes mellitus patients

Min Chen1, Jianying Yan1
Affiliations
  1. Department of Obstetrics, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China

open access

Ahead of Print
ORIGINAL PAPERS Obstetrics
Published online: 2023-03-10

Abstract

Objectives: To utilize an integrative strategy to construct functional miRNA-mRNA regulatory networks by combining the reverse expression relationships between miRNAs and targets and computational predictions for gestational diabetes mellitus (GDM).

Material and methods: A total of three microarray or RNA-seq datasets (GSE98043, GSE19649 and GSE92772) of plasma samples comparing GDM pregnant women and healthy control pregnant women were downloaded from the GEO database. The differentially expressed genes (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) was performed. The target genes of DEmiRNAs were identified using two independent and complementary types of information: computational target predictions and expression relationships. An interaction network was constructed to identify hub genes of GDM. Another dataset (GSE92772) was used to externally verify the predictive ability of the hub genes.

Results: A total of 264 DEmiRNAs and 1217 DEmRNAs were identified with Hsa-miR-146a-3p ranked first of DEmiRNAs. Functions of GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. A total of 47 target genes, including TRAF6, were shared between the computational target predictions and DEmRNAs and were identified as target genes of hsa-miR-146a-3p. The interaction network analysis identified TRAF6, CASP8, PTPN6, and CHD3 as hub genes involved in the pathophysiological process of GDM. Next, independent external validation was performed using the GSE19649 dataset. The expression of TRAF6, CASP8 and CHD3 in eight pairs of GDM blood samples was confirmed to be higher than that in healthy pregnant women blood samples with a AUC of 0.813, 0.813, and 0.703, respectively.

Conclusions: Our preliminary analysis revealed that miR-146a-3p/TRAF6 might play a central role in the pathogenesis of GDM. Three hub genes, TRAF6, CASP8, and CHD3, were identified and independently externally validated as potential GDM noninvasive serum markers for future biomarkers research.

Abstract

Objectives: To utilize an integrative strategy to construct functional miRNA-mRNA regulatory networks by combining the reverse expression relationships between miRNAs and targets and computational predictions for gestational diabetes mellitus (GDM).

Material and methods: A total of three microarray or RNA-seq datasets (GSE98043, GSE19649 and GSE92772) of plasma samples comparing GDM pregnant women and healthy control pregnant women were downloaded from the GEO database. The differentially expressed genes (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) was performed. The target genes of DEmiRNAs were identified using two independent and complementary types of information: computational target predictions and expression relationships. An interaction network was constructed to identify hub genes of GDM. Another dataset (GSE92772) was used to externally verify the predictive ability of the hub genes.

Results: A total of 264 DEmiRNAs and 1217 DEmRNAs were identified with Hsa-miR-146a-3p ranked first of DEmiRNAs. Functions of GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. A total of 47 target genes, including TRAF6, were shared between the computational target predictions and DEmRNAs and were identified as target genes of hsa-miR-146a-3p. The interaction network analysis identified TRAF6, CASP8, PTPN6, and CHD3 as hub genes involved in the pathophysiological process of GDM. Next, independent external validation was performed using the GSE19649 dataset. The expression of TRAF6, CASP8 and CHD3 in eight pairs of GDM blood samples was confirmed to be higher than that in healthy pregnant women blood samples with a AUC of 0.813, 0.813, and 0.703, respectively.

Conclusions: Our preliminary analysis revealed that miR-146a-3p/TRAF6 might play a central role in the pathogenesis of GDM. Three hub genes, TRAF6, CASP8, and CHD3, were identified and independently externally validated as potential GDM noninvasive serum markers for future biomarkers research.

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Keywords

gestational diabetes mellitus; miR-146a-3p; molecular markers; signaling pathway

About this article
Title

A preliminary integrated analysis of miRNA-mRNA expression profiles reveals a role of miR-146a-3p/TRAF6 in plasma from gestational diabetes mellitus patients

Journal

Ginekologia Polska

Issue

Ahead of Print

Article type

Research paper

Published online

2023-03-10

Page views

434

Article views/downloads

322

DOI

10.5603/GP.a2023.0017

Pubmed

36929799

Keywords

gestational diabetes mellitus
miR-146a-3p
molecular markers
signaling pathway

Authors

Min Chen
Jianying Yan

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