Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis

Abstract

Type 2 diabetes mellitus (T2dM) is a multifactorial and multigenetic disease, and its pathogenesis is complex and largely unknown. in the present study, microarray data (GSe201966) of β-cell enriched tissue obtained by laser capture microdissection were downloaded, including 10 control and 10 type 2 diabetic subjects. a comprehensive bioinformatics analysis of microarray data in the context of protein-protein interaction (PPi) networks was employed, combined with subcellular location information to mine the potential candidate genes for T2dM and provide further insight on the possible mechanisms involved. First, differential analysis screened 108 differentially expressed genes. Then, 83 candidate genes were identified in the layered network in the context of PPi via network analysis, which were either directly or indirectly linked to T2dM. of those genes obtained through literature retrieval analysis, 27 of 83 were involved with the development of T2dM; however, the rest of the 56 genes need to be verified by experiments. The functional analysis of candidate genes involved in a number of biological activities, demonstrated that 46 upregulated candidate genes were involved in 'inflammatory response' and 'lipid metabolic process', and 37 downregulated candidate genes were involved in 'positive regulation of cell death' and 'positive regulation of cell proliferation'. These candidate genes were also involved in different signaling pathways associated with 'Pi3K/akt signaling pathway', 'Rap1 signaling pathway', 'Ras signaling pathway' and 'MAPK signaling pathway', which are highly associated with the development of T2dM. Furthermore, a microrna (mir)-target gene regulatory network and a transcription factor-target gene regulatory network were constructed based on mirnet and networkanalyst databases, respectively. notably, hsa-mir-192-5p, hsa-mir-124-5p and hsa-mir-335-5p appeared to be involved in T2dM by potentially regulating the expression of various candidate genes, including procollagen c-endopeptidase enhancer 2, connective tissue growth factor and family with sequence similarity 105, member a, protein phosphatase 1 regulatory inhibitor subunit 1 a and cc motif chemokine receptor 4. Smad5 and Bcl6, as transcription factors, are regulated by ankyrin repeat domain 23 and transmembrane protein 37, respectively, which might also be used in the molecular diagnosis and targeted therapy of T2dM. Taken together, the results of the present study may offer insight for future genomic-based individualized treatment of T2dM and help determine the underlying molecular mechanisms that lead to T2dM.

Bioinformatic Reconstruction and Analysis of Gene Networks Related to Glucose Variability in Diabetes and Its Complications

“…The reconstruction and analysis of gene networks is a widely used approach for studying the mechanisms of complex biological processes and multifactorial diseases [ 25 , 26 ]. Specifically, this approach was applied for identification of key genes and pathways involved in pathogenesis of diabetes and its complications [ 27 , 28 , 29 , 30 ]. However, to our knowledge, GV-related networks have not been reconstructed and analyzed yet.…”

GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs

“…All others do not have enough data to determine whether they are expressed or not in the brain. Only four were previously associated with any neurological disease or with AD risk factors: hsa-miR-373-5p with schizophrenia ( Pala and Denkçeken, 2020 ); hsa-miR-657 with type 2 diabetes ( Lv et al, 2008 ); hsa-miR-192-5p with venous thrombosis and type 2 diabetes ( Lu et al, 2020 ; Rodriguez-Rius et al, 2020 ); and has-miR-147b with negative regulation of the inflammatory response ( van Scheppingen et al, 2018 ).…”

Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies

“…miR-92a-3p regulates insulin biosynthesis [ 43 ], and has a role in insulin secretion by pancreatic β cells [ 44 ], and in insulin stimulated glucose uptake by skeletal muscle [ 8 ]. MiR-192-5p appears to be involved in type 2 diabetes (T2DM) by regulating the expression of several genes involved in T2DM, such as procollagen C-endopeptidase enhancer 2 (PCOLCE2), which is significantly decreased in T2DM [ 45 , 46 ]. In healthy uncomplicated pregnancies miR-451a is constitutively expressed [ 41 ] however, our study found upregulation in the first trimester of pregnancies that went on to be diagnosed with GDM.…”