Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus

Background: Intrauterine exposure to gestational diabetes mellitus (GDM) poses significant risks to fetal development and future metabolic health. Despite its clinical importance, the role of microRNAs (miRNAs) in fetoplacental vascular endothelial cell (VEC) programming in the context of GDM remain...

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Main Authors: Yulan Lu, Chunhong Liu, Xiaoxia Pang, Xinghong Chen, Chunfang Wang, Huatuo Huang
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580824002528
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author Yulan Lu
Chunhong Liu
Xiaoxia Pang
Xinghong Chen
Chunfang Wang
Huatuo Huang
author_facet Yulan Lu
Chunhong Liu
Xiaoxia Pang
Xinghong Chen
Chunfang Wang
Huatuo Huang
author_sort Yulan Lu
collection DOAJ
description Background: Intrauterine exposure to gestational diabetes mellitus (GDM) poses significant risks to fetal development and future metabolic health. Despite its clinical importance, the role of microRNAs (miRNAs) in fetoplacental vascular endothelial cell (VEC) programming in the context of GDM remains elusive. This study aims to identify signature miRNA genes involved in this process using bioinformatics analysis via multiple algorithms. Methods: The dataset used in this study was acquired from Gene Expression Omnibus (GEO). Firstly, differentially expressed miRNA genes (DEMGs) were evaluated using limma package. Thereafter, an enrichment analysis of DEMGs was performed. Then, the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) were used as the other algorithms for screening candidate signature miRNA genes. Genes from the intersection of limma, LASSO, and SVM genes were used as the final signature miRNA genes. The receiver operator characteristic curve (ROC), the nomogram diagram, gene set enrichment analysis (GSEA), and signature miRNAs-target genes interaction network were implemented further to explore the features and functions of signature genes. Results: A total of 32 DEMGs, with 21 upregulated and 11 downregulated miRNA genes, were obtained from limma analysis. LASSO and SVM analyses identified 15 and 12 candidate signature miRNA genes, respectively. After the intersection of genes from limma, LASSO, and SVM analyses, MIR34A and MIR186 were found as the final signature genes related to fetoplacental VEC programming. MIR34A and MIR186 were highly expressed and were associated with an increased risk of fetoplacental VEC programming in GDM mothers. The area under the curve (AUC) of ROC for MIR34A and MIR186 were 0.960 and 0.935, respectively. GSEA analysis revealed that these signature genes positively participate in cellular processes related to VEC migration, cell differentiation, angiogenesis, programmed cell death, and inflammatory response. Finally, miRNAs-target genes interaction network analysis provides the interaction of signature miRNAs and their critical target genes, which may help further studies for miR-34a and miR-186 in GDM. Conclusions: MIR34A and MIR186 are novel signature miRNA genes related to fetoplacental VEC programming that may represent critical genes associated with placental function and fetal programming under GDM conditions.
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spelling doaj-art-75c2b4f2097f4726b29b141ead7dd3ab2025-08-20T02:03:07ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-014110188810.1016/j.bbrep.2024.101888Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitusYulan Lu0Chunhong Liu1Xiaoxia Pang2Xinghong Chen3Chunfang Wang4Huatuo Huang5Center of Reproduction Medical, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, ChinaCenter for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Guangxi, 533000, ChinaCenter for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Guangxi, 533000, ChinaCenter of Reproduction Medical, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, ChinaCenter for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Guangxi, 533000, China; Corresponding author. Center for Medical Laboratory Science, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.Center for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Guangxi, 533000, China; Corresponding author. Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Guangxi, 533000, China.Background: Intrauterine exposure to gestational diabetes mellitus (GDM) poses significant risks to fetal development and future metabolic health. Despite its clinical importance, the role of microRNAs (miRNAs) in fetoplacental vascular endothelial cell (VEC) programming in the context of GDM remains elusive. This study aims to identify signature miRNA genes involved in this process using bioinformatics analysis via multiple algorithms. Methods: The dataset used in this study was acquired from Gene Expression Omnibus (GEO). Firstly, differentially expressed miRNA genes (DEMGs) were evaluated using limma package. Thereafter, an enrichment analysis of DEMGs was performed. Then, the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) were used as the other algorithms for screening candidate signature miRNA genes. Genes from the intersection of limma, LASSO, and SVM genes were used as the final signature miRNA genes. The receiver operator characteristic curve (ROC), the nomogram diagram, gene set enrichment analysis (GSEA), and signature miRNAs-target genes interaction network were implemented further to explore the features and functions of signature genes. Results: A total of 32 DEMGs, with 21 upregulated and 11 downregulated miRNA genes, were obtained from limma analysis. LASSO and SVM analyses identified 15 and 12 candidate signature miRNA genes, respectively. After the intersection of genes from limma, LASSO, and SVM analyses, MIR34A and MIR186 were found as the final signature genes related to fetoplacental VEC programming. MIR34A and MIR186 were highly expressed and were associated with an increased risk of fetoplacental VEC programming in GDM mothers. The area under the curve (AUC) of ROC for MIR34A and MIR186 were 0.960 and 0.935, respectively. GSEA analysis revealed that these signature genes positively participate in cellular processes related to VEC migration, cell differentiation, angiogenesis, programmed cell death, and inflammatory response. Finally, miRNAs-target genes interaction network analysis provides the interaction of signature miRNAs and their critical target genes, which may help further studies for miR-34a and miR-186 in GDM. Conclusions: MIR34A and MIR186 are novel signature miRNA genes related to fetoplacental VEC programming that may represent critical genes associated with placental function and fetal programming under GDM conditions.http://www.sciencedirect.com/science/article/pii/S2405580824002528PregnancyPlacentaBioinformaticsFetusVascular endothelial cellsDevelopment programming
spellingShingle Yulan Lu
Chunhong Liu
Xiaoxia Pang
Xinghong Chen
Chunfang Wang
Huatuo Huang
Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
Biochemistry and Biophysics Reports
Pregnancy
Placenta
Bioinformatics
Fetus
Vascular endothelial cells
Development programming
title Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
title_full Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
title_fullStr Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
title_full_unstemmed Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
title_short Bioinformatic identification of signature miRNAs associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
title_sort bioinformatic identification of signature mirnas associated with fetoplacental vascular dysfunction in gestational diabetes mellitus
topic Pregnancy
Placenta
Bioinformatics
Fetus
Vascular endothelial cells
Development programming
url http://www.sciencedirect.com/science/article/pii/S2405580824002528
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