Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

Abstract

BackgroundRegardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics.ResultsThe use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis.ConclusionsThese results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.

Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets

“…Many of these shared miRNAs have been associated with metabolic pathways, immunological processes, and tumorigenesis. Recent data confirmed that nine miRNAs were shared among the three types of diabetes, including hsa-miR-126, hsa-miR-144, hsa-miR-27a, hsa-miR-29b, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-199a-5p, and hsa-miR-342-3p (Collares et al 2013). Thus, the aim of the study was to identify miRNAs whose activities changed in epicardial adipose tissue during hyperglycemia in piglets.…”

“…It has been proposed that peripheral blood mononuclear cells can be used as reporter cells to characterize the miR expression profiling during type 1 (T1D) and type 2 diabetes mellitus (T2D) and gestational diabetes mellitus. Collares and coworkers evaluated shared miRNAs among the major types of diabetes, including hsa-miR-29b, miR-142-3p, and hsa-miR-142-5p (Collares et al 2013). Many of these shared miRNAs have been associated with metabolic pathways, immunological processes, and tumorigenesis.…”

Circulating microRNAs and diabetes: potential applications in medical practice

“…This suggests that there is a distinct pattern of circulating miRNAs in type 1 diabetes vs type 2 diabetes. Indeed, a study comparing miRNA profiles between type 1 diabetes, type 2 diabetes and GDM in peripheral blood mononuclear cells confirmed divergent profiles in the different forms of diabetes despite the fact that a few miRNAs are shared among the three groups [70].…”

“…Several studies have reported that acute physical activity and prolonged exercise training programmes can modify the circulating miRNA profile [87]. Furthermore, smoking appears to alter the pattern of circulating miRNAs [88][89][90][91], and of the miRNAs affected, miR-29b was identified to be deregulated in diabetic patients [27,28,70]. Environmental exposure to air pollutants and chemicals seems to modify circulating miRNAs [92], inducing a bias that is difficult to estimate.…”

“…Several studies have identified age-related modifications in circulating miRNA levels [77][78][79][80][81][82]. Notably, among these, miR-29b [27,28,70], miR-130b [31], miR-222 [31], miR-375 [22], miR-21 [26,27,36] and miR-126 [23,27,30,31] were found to be deregulated in diabetic patients. These results underline that age could induce a bias, which has to be dealt with.…”