MicroRNA profiling and their pathways in South African individuals with prediabetes and newly diagnosed type 2 diabetes mellitus

Abstract

Early identification of individuals with elevated risk of developing diabetes mellitus, followed by the implementation of effective prevention interventions can delay the onset of the disease and related complications. In this regard, recent studies have shown that miRNAs are useful as early markers of certain disease types, including diabetes. We used high throughput sequencing to assess miRNA expression profiles from whole blood of 12 individuals with screen-detected diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for age, blood pressure, smoking and body mass index. We identified a total of 261 (57 novel) differentially expressed miRNA profiles between the study groups. Comparison of the miRNA expression profiles between prediabetess and diabetes revealed 25 common miRNA, but highlighted some interesting differences. For instance, three miRNAs (miR-126-3p, miR-28-3p miR-486-5p) were dysregulated in prediabetes compared to screen-detected diabetes. Target gene analysis showed thousands of potential genes and KEGG pathway analysis revealed 107 significant pathways of which some are involved signal transduction, cell-cell communications, cell growth and death, immune response, endocrine system and metabolic diseases. This first detailed African study has shown both known and novel differentially expressed miRNAs in relation to glucose tolerance.

Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer

“…Dysregulated miRNAs between prediabetes and DM could be identified and regarded as potential biomarkers to screen people at high risk of developing diabetes. For instance, circulating miR-486-5p/miR-486 were found to be downregulated in patients with DM as compared to healthy controls [70,71]. MiR-486-5p was also downregulated in diabetes patients, as compared to individuals with IGT, suggesting it plays a role in the development of DM from prediabetes [70].…”

“…For instance, circulating miR-486-5p/miR-486 were found to be downregulated in patients with DM as compared to healthy controls [70,71]. MiR-486-5p was also downregulated in diabetes patients, as compared to individuals with IGT, suggesting it plays a role in the development of DM from prediabetes [70]. In Asian Indians, a high risk population for DM, miR-486 is a protective factor for reducing glycemic progression and is negatively associated with the development of glycemic impairment (OR 0.5 (0.3-0.8), p < 0.01) [71].…”

Circulating miR-30a-5p and miR-182-5p in Prediabetes and Screen-Detected Diabetes Mellitus

“…[11][12][13] Both miRNAs have also displayed dysregulation in hyperglycaemic individuals. 14 Comprehensive analysis of specific miRNA signatures may shed light on the complex mechanisms involved with the progression of DM. Therefore, in this study, we aimed to investigate the expression of these two miRNAs across glucose tolerance status in a South African population previously reported to have a high prevalence of undiagnosed diabetes.…”

Investigation of Candidate Genes and Mechanisms Underlying Obesity Associated Type 2 Diabetes Mellitus Using Bioinformatics Analysis and Screening of Small Drug Molecules&nbsp;

“…Eberlé et al [165], Cheng et al [166], Cavallari et al [167], Qi et al [168] and Yan et al [169] indicated that SREBF1, MBD2, IRF4, CREB1 and RELA (Nuclear factor-kB) were responsible for advancement of obesity associated type 2 diabetes mellitus. Matsha et al [170] and Ding et al [171] demonstrated that hsa-mir-1299 and hsa-mir-4530 were liable for progression of type 2 diabetes mellitus. Hall et al [172] and Salazar-Mendiguchía et al [173] reported that FLNC ( lamin C) and TRIM63were involved in progression of cardio vascular disease, but these genes might be essential for development of obesity associated type 2 diabetes mellitus.…”