Increased Expression of Circulating microRNA 101-3p in Type 1 Diabetes Patients: New Insights Into miRNA-Regulated Pathophysiological Pathways for Type 1 Diabetes

Abstract

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.

MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States

“…miR-378a-3p correlated negatively to IA2A and ZnT8A(Trp) but positively with GAD autoantibodies [17]. In a different autoantibody-positive cohort, miR-101-3p was elevated only in non-diabetic children with multiple autoantibodies and in children with recent-onset T1D and also correlated positively with GAD autoantibody levels [18]. In this cohort, miR-204-5p was elevated only in children with recent-onset T1D but not in non-diabetic autoantibody-positive children.…”

Dysregulated Circulating micro RNAs Markers: New Evidence into Expression Pattern in Children with T1D among Egyptian Population

“…This process could be served as a new therapeutically tried target for T1DM [30,31]. matter that was largely analyzed by Santos A et al, who reported that the expression of miR-101 was about 3fold higher in patients with multiple autoantibodies level [32].…”

mir-101-3p Downregulation Promotes Fibrogenesis by Facilitating Hepatic Stellate Cell Transdifferentiation During Insulin Resistance

“…Zheng Y. and colleagues found that miR-101a is enriched in pancreatic cells and participates in β-cell dysfunction by decreasing the expression of antiapoptotic Bcl-2 and reducing pancreatic insulin secretion [30]. Higher circulating levels of miR-101-3p have also been reported to be associated with early-onset of T1D and T2D [31,32]. Therefore, the tissue expression of several miRNAs could be a consequence of a dynamic regulation of the rate of miRNAs produced and released into the circulation [4].…”