Dataset Information

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes.

ABSTRACT: We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A_1c (HbA_1c), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time PCR was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miRNAs replicated in both panels and 4 with high statistical significance. The strongest positive correlations with HbA_1c were found with miR-125b-5p (r_s = 0.40, P = 6.0 × 10^-5) and miR-365a-3p (r_s = 0.35, P = 5.9 × 10^-4). The strongest negative correlations were found with miR-5190 (r_s = -0.30, P = 0.003) and miR-770-5p (r_s = -0.27, P = 0.008). Pathway analysis revealed that 50 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched by genes targeted by these four miRNAs. The axon guidance signaling pathway was enriched (P < 1 × 10^-7) by genes targeted by all four miRNAs. In addition, three other pathways (Rap1 signaling, focal adhesion, and neurotrophin signaling) were also significantly enriched but with genes targeted by only by three of the identified miRNAs. In conclusion, our study identified four circulating miRNAs that were influenced by variation in hyperglycemia. Dysregulation of these miRNAs, which are associated with hyperglycemia in patients with T1D, may contribute to the development of diabetes complications. However, there are multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of diabetes complications.

SUBMITTER: Satake E

PROVIDER: S-EPMC5910001 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes.

Satake Eiichiro E Pezzolesi Marcus G MG Md Dom Zaipul I ZI Smiles Adam M AM Niewczas Monika A MA Krolewski Andrzej S AS

Diabetes 20180216 5

We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time PCR was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miR ...[more]

PMID: 29453204

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Project description:MicroRNAs (miRs) are master regulators of post-transcriptional gene expression, and they are often dysregulated in individuals suffering from diabetes. We investigated the roles of miR-101-3p and miR-204-5p, both of which negatively regulate insulin secretion and cell survival and are highly expressed in pancreatic β cells, in the context of type 1 diabetes (T1D) pathogenesis. Using quantitative real time PCR, we evaluated serum levels of miR-101-3p and miR-204-5p in four groups, including recent-onset T1D patients (T1D group; n = 50), individuals with normal glucose levels expressing one islet autoantibody (Ab) (single Ab group; n = 26) or multiple autoantibodies (multiple Ab group; n = 12), and healthy controls (control group; n = 43). An in silico analysis was performed to identify potential target genes of these miRNAs and to delineate enriched pathways. The relative expression of serum miR-101-3p was approximately three times higher in the multiple Ab and T1D groups than that in the single Ab and control groups (p < 0.0001). When considering all groups together, miR-101-3p expression was positively correlated with the level of islet autoantibodies GADA (r = 0.267; p = 0.0027) and IA-2A (r = 0.291; p = 0.001), and the expression of the miRNA was not correlated with levels of ZnT8A (r = 0.125; p = 0.183). miR-101-3p expression did not correlate with HbA1c (r = 0.178; p = 0.052) or glucose levels (r = 0.177; p = 0.051). No significant differences were observed in miR-204-5p expression among the analyzed groups. Computational analysis of the miR-101-3p target gene pathways indicated a potential activation of the HGF/c-Met, Ephrin receptor, and STAT3 signaling pathways. Our study demonstrated that the circulating levels of miR-101-3p are higher in T1D patients and in individuals with normal glucose levels, testing positive for multiple autoantibodies, indicating that miR-101-3p precedes loss of glucose homeostasis. The pathogenic role of miR-101-3p in T1D may involve multiple molecular pathways.

Dataset Information

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes.

Publications

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes.

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