Accepted for/Published in: JMIR Bioinformatics and Biotechnology
Date Submitted: Jul 28, 2021
Date Accepted: Dec 27, 2021
Multi-omics Integration and Interactomics Reveal Novel Molecular Networks and Regulatory MicroRNAs in Type 2 Diabetes Mellitus
ABSTRACT
Background:
Type 2 diabetes mellitus (T2DM) is a metabolic disorder with severe co-morbidities. A multi-omics approach can facilitate the identification of novel therapeutic targets and biomarkers with proper validation of potential microRNA (miRNA) interaction.
Objective:
The study aimed at the identification of significantly expressed target genes and their regulating miRNAs using publicly available gene expression omnibus (GEO) datasets of T2DM using in-silico analysis.
Methods:
Using computational bioinformatics, differentially expressed genes (DEGs) from five publicly available datasets GSE38642, GSE25724, GSE20966, GSE26887, and GSE23343 were analyzed. Further, in-silico analysis was done for functional enrichment analysis, protein-protein interaction, and miRNA-mRNA interactions.
Results:
We extracted 2852, 8631, 5501, 3662 and 3753 DEGs from expression profile datasets GSE38642, GSE25724, GSE20966, GSE26887, and GSE23343, respectively. DEGs analysis showed that 16 co-exist genes enriched in Insulin Secretion, Endocrine Resistance, T2DM related Pathway. Four DEGs MAML3, EEF1D, NRG1, and CDK5RAP2 were important mRNAs in the cluster network that were regulated by commonly targeted miRNAs (hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-124-3p, hsa-mir-1-3p) which were involved in the AGE-RAGE signaling pathway culminating in diabetic complications and endocrine resistance.
Conclusions:
The present study revealed significantly enriched dysregulated pathways in T2DM. Integration of overlapped genes with various biomolecular interaction networks yielded 16 seed genes involved in the pathophysiology of T2DM in various tissues. Nevertheless, some critical genes GNAQ, PCDH7, CDK5RAP2, NPC1, OXR1, TRAK1, PSIP1, NRG1 and AGE-RAGE signaling pathway in diabetic complication and endocrine resistance are novel, in the sense that they have not previously been shown to be extensively important in T2DM. Furthermore, we have sorted miRNAs (hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-124-3p, hsa-mir-1-3p) known to contribute to T2DM and its complications through different pathways. Thus, the present study provides a network signature for the pancreas, liver, and heart in T2DM.
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