Type 1 diabetes (T1D) is an autoimmune disorder which is characterized by autoimmune attack on β cells of pancreas and lack of insulin. The involvement of microRNAs (miRNAs) in the development of immune system and their differential expression in various autoimmune diseases including T1D have been well established. In this study, the association between expression levels of miR-20a, miR-326 and T1D were evaluated. The expression levels of miR-20a and miR-326 were measured in the PBMCs of 21 T1D patients and 16 healthy controls using qPCR method. In silico analysis was also performed on targetome of miR-20a and miR-326. Both miR-20a (p value: 0.015) and miR-326 (p value: 0.005) were upregulated in the PBMCs of T1D patients compared to healthy controls. Furthermore, different dysregulated miR326–mRNA and miR20a–mRNA interactions were also suggested using integrative computational analysis. The expression level of miR-20a and miR-326 indicates significant association with T1D which suggests the possible regulatory effects of these non-coding RNAs in T1D.
MicroRNA Type 1 diabetes miR-20a miR-326
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This study was performed at the biology department of University of Isfahan and was funded by the graduate office of the University of Isfahan.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study is approved by the University of Isfahan review board (Agreement Number: 94/34330) and also the ethics committee of Shariati Hospital, Isfahan, Iran (Agreement Number: 154/92/23273). A written consent form was obtained from each patient according to the Declaration of Helsinki. A written informed consent was also obtained from healthy control subjects who were above the 16 years old. In addition, the blood samples of patients and healthy controls with age less than 16 years, were collected with full written informed parent’s consent and in compliance with the ethical protocol and standards of Shariati Hospital.
Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13(8):622–638PubMedGoogle Scholar
Guay C, Regazzi R (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9(9):513–521PubMedGoogle Scholar
Hezova R et al (2010) microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cell Immunol 260(2):70–74PubMedGoogle Scholar
Nielsen LB et al (2012) Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res 2012: 896362PubMedPubMedCentralGoogle Scholar
Salas-Pérez F et al (2013) MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes. Immunobiology 218(5):733–737PubMedGoogle Scholar
Takahashi P et al (2014) MicroRNA expression profiling and functional annotation analysis of their targets in patients with type 1 diabetes mellitus. Gene 539(2):213–223PubMedGoogle Scholar
Dweep H et al (2011) miRWalk—database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 44(5):839–847PubMedPubMedCentralGoogle Scholar
Mogilyansky E, Rigoutsos I (2013) The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 20(12):1603–1614PubMedPubMedCentralGoogle Scholar
Du C et al (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10(12):1252–1259PubMedPubMedCentralGoogle Scholar
Sun X-G et al (2016) Negative correlation between miR-326 and Ets-1 in regulatory T cells from new-onset SLE patients. Inflammation 39(2):822–829PubMedGoogle Scholar
Guan H et al (2013) MicroRNA let-7e is associated with the pathogenesis of experimental autoimmune encephalomyelitis. Eur J Immunol 43(1):104–114PubMedPubMedCentralGoogle Scholar
Honardoost MA et al (2014) miR-326 and miR-26a, two potential markers for diagnosis of relapse and remission phases in patient with relapsing–remitting multiple sclerosis. Gene 544(2):128–133PubMedGoogle Scholar
Gillespie KM (2006) Type 1 diabetes: pathogenesis and prevention. Can Med Assoc J 175(2):165–170Google Scholar
Baumjohann D, Ansel KM (2013) MicroRNA-mediated regulation of T helper cell differentiation and plasticity. Nat Rev Immunol 13(9):666–678PubMedPubMedCentralGoogle Scholar
Bronevetsky Y et al (2013) T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire. J Exp Med 210(2):417–432PubMedPubMedCentralGoogle Scholar
Wu T et al. (2012) Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation. Proc Natl Acad Sci USA 109(25):9965–9970PubMedGoogle Scholar
Ventura A et al (2008) Targeted deletion reveals essential and overlapping functions of the miR-17∼ 92 family of miRNA clusters. Cell 132(5):875–886PubMedPubMedCentralGoogle Scholar
Xiao C et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9(4):405–414PubMedPubMedCentralGoogle Scholar
Snowhite IV et al. (2017) Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes. Diabetologia 60(8):1409–1422PubMedPubMedCentralGoogle Scholar
Cox MB et al (2010) MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS ONE 5(8):e12132PubMedPubMedCentralGoogle Scholar
Teruel R et al (2011) Identification of miRNAs as potential modulators of tissue factor expression in patients with systemic lupus erythematosus and antiphospholipid syndrome. J Thromb Haemost 9(10):1985–1992PubMedGoogle Scholar
Carlsen AL et al (2013) Circulating microRNA expression profiles associated with systemic lupus erythematosus. Arthritis Rheum 65(5):1324–1334PubMedGoogle Scholar
Vereecke L, Beyaert R, van Loo G (2011) Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. Biochem Soc Trans 39(4):1086–1091PubMedGoogle Scholar
Størling J, Pociot F (2017) Type 1 diabetes candidate genes linked to pancreatic islet cell inflammation and beta-cell apoptosis. Genes 8(2):72PubMedCentralGoogle Scholar
Duan R et al (2010) Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS. Ann Rheum Dis 69(9):1724–1729PubMedGoogle Scholar
Poy MN et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432(7014):226–230PubMedGoogle Scholar
Corvol J-C et al. (2008) Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proc Natl Acad Sci USA 105(33):11839–11844PubMedGoogle Scholar
Łuczyński W et al (2009) Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. Acta Biochim Pol 56(2):361–370PubMedGoogle Scholar
Ji N, Sosa RA, Forsthuber TG (2011) More than just a T-box: the role of T-bet as a possible biomarker and therapeutic target in autoimmune diseases. Immunotherapy 3(3):435–441PubMedPubMedCentralGoogle Scholar
Barrett JC et al (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41(6):703–707PubMedPubMedCentralGoogle Scholar
Hunter K et al (2007) Interactions between Idd5. 1/Ctla4 and other type 1 diabetes genes. J Immunol 179(12):8341–8349PubMedGoogle Scholar