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Analysis of Micro-RNAs and Gene Expression Profiles in Gestational Diabetes Mellitus: A Consensus Approach

Author(s): R. Bhushan, A. Rani, D. Gupta, I. Khan, A. Tripati, R. P. Singh and K. D. Pawan

Gestational Diabetes Mellitus (GDM) is a metabolic disorder characterized by insulin resistance. Lack of complete mechanisms involved in its pathophysiology makes its early diagnosis and treatment a difficult task. Recently, micro-RNAs are associated with many diseases including GDM. Its high stability in biological fluids and the ability to modulate genes at large scale makes it potent bio-markers. Here, we analyzed the transcriptomic datasets (GSE98043 and GSE19649) to gain a deeper understanding of the role of miRNAs in GDM. We processed and analyzed the microarray datasets to find differentially expressed miRNAs. Then we used a consensus approach to find the predicted as well as validated GDM related target genes. We then constructed the miRNA-mRNA gene regulatory module to have a better understanding of its regulation. These target genes were further enriched for their functions and pathways. We identified a total of 128 DE miRNAs, of which the top 20 were selected for downstream processing, and 49 validated GDM related target genes among predicted ones that may contribute to the regulatory alterations behind GDM. The micro-RNAs were linked to carbohydrate metabolism, insulin signaling, and cell proliferation and apoptosis. We then focused on miRNAs which were regulating most of the genes related to GDM, this lead to the identification of four potential GDM miRNAs biomarkers, miR-3065-3p, miR-4650-3p, miR-29b-2-5p and miR-3915 that were significantly altered in GDM. The pathways enrichment analysis shows that they are involved in insulin signaling and pathways related to cancer. We demonstrated the most regulatory and novel miRNAs, miRNA-mRNA interactions, and their related pathways in GDM using Bioinformatics methods. Accordingly, our defined miRNAs and genes could be used for future molecular studies and can be useful in early diagnosis and treatment of GDM.