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Lookup NU author(s): Dr Long Xie
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026.Purpose: Gestational diabetes mellitus (GDM) significantly threatens maternal and fetal health, necessitating early and accurate diagnostic tools. This study aimed to identify and validate circulating microRNAs (miRNAs) as novel biomarkers for GDM. Methods: A two-phase cross-sectional study enrolled 55 GDM patients and 55 matched healthy pregnant controls. In the discovery phase, RNA sequencing (RNA-seq) of peripheral blood RNA from a randomly selected subset (5 GDM patients, 5 controls) identified differentially expressed miRNAs. The validation phase employed reverse transcription and quantitative PCR (qPCR) in the entire cohort to confirm identified miR-326 and miR-532-3p expression. Bioinformatics analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) investigated their functional roles using a consensus-based approach across multiple databases. Results: RNA-seq revealed significant upregulation of miR-326 (mean normalized counts = 14.59, P < 0.05; log2[Fold Change] = 0.93, P < 0.01) and miR-532-3p (mean normalized counts = 46.45, P < 0.05; log2[Fold Change] = 0.66, P < 0.01) in GDM patients, a finding corroborated by cross-referencing with the Gene Expression Omnibus (GEO) database. qPCR validation confirmed significantly higher expression for both miRNAs in GDM (P < 0.001), with strong negative correlations to fasting, 1-hour and 2-hour postprandial glucose levels. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic performance (area under the curve [AUC]: 0.95 [95% CI: 0.91–0.99] for miR-326 and 0.96 [95% CI: 0.93–0.99] for miR-532-3p), robustly confirmed by bootstrap resampling. Functional analyses linked these miRNAs to phosphoinositide 3-kinase (PI3K)/Akt and Rap1 signaling pathways. Conclusion: This study provides compelling evidence for circulating miR-326 and miR-532-3p as a synergistic pair of biomarkers for GDM. Their high diagnostic accuracy and mechanistic insights into metabolic dysregulation position them as a promising complementary tool for early GDM risk assessment and for understanding GDM pathophysiology.
Author(s): Lin H-Z, Liang Z-K, Huang J-J, Yang Y, Huang Y, Wu Z-S, Tan J-L, Huang S, Ruan S-H, Xu B-Y, Ruan Z-F, Huang T-S, Wang Q-G, Xie L
Publication type: Article
Publication status: Published
Journal: Journal of Endocrinological Investigation
Year: 2026
Pages: epub ahead of print
Online publication date: 05/02/2026
Acceptance date: 23/01/2026
Date deposited: 23/02/2026
ISSN (print): 0391-4097
ISSN (electronic): 1720-8386
Publisher: Springer Science
URL: https://doi.org/10.1007/s40618-026-02829-z
DOI: 10.1007/s40618-026-02829-z
Data Access Statement: The manuscript encompasses all necessary data. Raw experimental data, including export files of RNA-seq, PCR reactions, and derived data supporting the findings of this study can be available from the corresponding authors H-Z. L and L. X upon reasonable request
PubMed id: 41642434
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