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

Author(s)

Santos, Aritania S. ^[1] ; Neto, Edecio Cunha ^{[2, 3, 4]} ; Fukui, Rosa T. ^[1] ; Ferreira, Ludmila R. P. ^[5] ; Silva, Maria Elizabeth R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Carboidratos Radioimunoensios LIM 18, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo - Brazil

^[3] Natl Inst Sci & Technol Iii INCT, Inst Invest Immunol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy LIM60, Sao Paulo - Brazil

^[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, RSBL, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 10, JUL 23 2019.
• Web of Science Citations: 2

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 b 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) ormultiple 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. (AU)

• FAPESP's process: 14/15971-4 - Serum expression of microRNAs in type 1 autoimmune Diabetes
• Grantee: Maria Elizabeth Rossi da Silva
• Support Opportunities: Regular Research Grants