Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus.

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Data of mRNA and miRNA expression microarray (GSE103552 and GSE104297) and DNA methylation data set (GSE106099) were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated genes (DMGs) were obtained by limma package. Functional and enrichment analyses were performed with the DAVID database. The protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Simultaneously, a connectivity map (CMap) analysis was performed to screen potential therapeutic agents for GDM. In GDM, 184 low miRNA-targeting up-regulated genes and 234 high miRNA-targeting down-regulated genes as well as 364 hypomethylation-high-expressed genes and 541 hypermethylation-low-expressed genes were obtained. They were mainly enriched in terms of axon guidance, purine metabolism, focal adhesion and proteasome, respectively. In addition, 115 genes (67 up-regulated and 48 down-regulated) were regulated by both aberrant alternations of miRNAs and DNA methylation. Ten chemicals were identified as putative therapeutic agents for GDM and four hub genes (IGF1R, ATG7, DICER1 and RANBP2) were found in PPI and may be associated with GDM. Overall, this study identified a series of differentially expressed genes that are associated with epigenetic alternations of miRNA and DNA methylation in GDM. Ten chemicals and four hub genes may be further explored as potential drugs and targets for GDM diagnosis and treatment, respectively.", "claims": [{"id": "claim-method", "statement": "After background correction, logarithm transformation and normalization were conducted, differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylation probes (DMPs) were screened by using the limma package in R (version 3.6.0).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33085184", "locator": "sections[4] \"Data process\" paragraph 2", "quote": "After background correction, logarithm transformation and normalization were conducted, differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylation probes (DMPs) were screened by using the limma package in R (version 3.6.0)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that the data supporting the findings of this study are available within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33085184", "locator": "sections[30] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The authors declare that the data supporting the findings of this study are available within the article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33085184"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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