Abstract
Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women, posing significant risks to the life and health of both mothers and fetuses. With improving living standards, the incidence of GDM is increasing rapidly. Therefore, understanding the underlying mechanism of GDM is of paramount importance. We downloaded two datasets from the Gene Expression Omnibus (GEO) database, containing sequencing data specifically related to “gestational diabetes” and “placenta”. By merging these two datasets, a mRNA expression dataset was obtained and subjected to bioinformatics analyses. To screen out corresponding genes, differential analysis and weighted correlation network analysis (WGCNA) were carried out. Lasso, support vector machine and random forest analyses were subsequently performed for identifying key genes from the differentially expressed genes (DEGs) jointly screened out through differential analysis and WGCNA. Afterwards, immunoinfiltration and correlation analysis were performed to screen immune cells that play a role in disease progression and explore the correlation between the screened key genes and immune cells, after which Western Blot, quantitative real-time polymerase chain reaction, Immunohistochemistry, methyl thiazolyl tetrazolium, flow cytometry, scratch and Transwell assays were, respectively, performed for verification. For further verification, we found that the expression levels of MAP6D1 and SCUBE1 in embryonic tissues of GDM patients was higher compared to those of healthy pregnant women, which was consistent with the results of bioinformatics analysis. Consequently, SCUBE1 was selected for follow-up experiment. In order to explore the role of SCUBE1 in the development of GDM, we treated the trophoblastic cells HTR-8/SVneo with high glucose, and on this basis downregulated the expression of SCUBE1. Through further analysis, we observed that SCUBE1 had a role in reducing cell activity, migration and invasion, and promoting cell apoptosis. In summary, SCUBE1 promotes the development of GDM by increasing cell apoptosis and reducing cell activity, migration, and invasion.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- GDM:
-
Gestational diabetes mellitus
- GEO:
-
Gene Expression Omnibus
- WGCNA:
-
Weighted correlation network analysis
- SRA:
-
Sequence read archive
- WB:
-
Western Blot
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- IHC:
-
Immunohistochemistry
- DEGs:
-
Differentially expressed genes
- GO:
-
Gene Ontology
- BP:
-
Biological process
- CC:
-
Cellular component
- MF:
-
Molecular function
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- SVM:
-
Support vector machine
- HG:
-
High glucose
- NG:
-
Normal glucose
- MTT:
-
Methyl thiazolyl tetrazolium
- SD:
-
Standard deviation
- MAE:
-
Mean absolute error
- NES:
-
Normalized enrichment score
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Funding
This work was supported by Jinhua Science and Technology Planning Project (No. 2021-4-219), and Zhejiang Medical and Health Science and Technology Planning Project (No. 2021KY854).
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JL made substantial contributions to the conception and design of the work, performed formal analysis, and drafted the work and substantively revised it. CL performed data analysis, prepared figures and tables, and substantively revised the manuscript. All authors have approved the submitted version.
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Liu, J., Lu, C. SCUBE1 Promotes Gestational Diabetes Mellitus: A Bioinformatics and Experimental Investigation. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10769-7
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DOI: https://doi.org/10.1007/s10528-024-10769-7