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Circulating miRNA-375 levels are increased in autoantibodies-positive first-degree relatives of type 1 diabetes patients

  • L. Bertoccini
  • F. Sentinelli
  • M. Incani
  • D. Bailetti
  • F. A. Cimini
  • I. Barchetta
  • A. Lenzi
  • M. G. Cavallo
  • E. Cossu
  • M. G. BaroniEmail author
Short Communication

Introduction

Growing evidence suggests that microRNAs (miRNAs) play a key role in immune system functions as well as in beta-cell metabolism, proliferation, and apoptosis, all processes involved in the pathogenesis of type 1 diabetes (T1D) [1].

MicroRNAs are a class of small noncoding RNAs of 19–22 nucleotides, which act as negative regulators of gene expression by partially pairing to the 3′ or 5′ untranslated regions of their target mRNAs [2]. Recent studies have demonstrated that miRNAs are detected not only inside cells but also in extracellular fluids and body secretions [2]. MiRNAs are secreted by cells via exosomes, and travel in the circulation attached to high-density lipoprotein particles, where cells can take them up through receptor-mediated endocytosis [3]. Blood miRNA levels have been proposed as a new class of biomarkers for diagnosis and prognosis of several diseases, including T1D, and also as new targets for treatments and interventions [4].

Although dysregulated...

Keywords

MicroRNAs Autoantibodies c-Peptide Sardinia Beta-cells Autoimmunity 

Abbreviations

Aabs

Autoantibodies

AUC

Area under the curve

Ct

Cycle threshold

FDR

First-degree relatives

GADA

Acid decarboxylase autoantibodies

IA2

Tyrosine phosphatase autoantibodies

IAA

Insulin autoantibodies

IGR

Impaired glucose regulation

miRNAs

MicroRNAs

ROC

Receiver operating characteristic

T1D

Type 1 diabetes

ZnT8A

Zinc transporter 8 autoantobodies

Notes

Acknowledgements

Particular thanks to C. Serafini, C. Satta, L. Perra, F. Scano, A. Strazzera (University Policlinic of Cagliari, Italy), P. Frongia, R. Ricciardi, C. Ripoli (San Michele Hospital, Cagliari), and M. Soro (San Martino Hospital, Oristano).

Author contributions

LB, FS, and MGB conceived and designed the study. LB, MI, and FS conducted the experiments. EC recruited the study population. LB, FS, FAC, DB, and IB analyzed and interpreted the data. LB, FS, and MGB wrote the manuscript. MGB, MGC, and EC revised critically and approved the manuscript.

Funding

Financial support was provided by the following institutions: Regione Autonoma della Sardegna RAS 2007 (number CRP-59453), Sapienza Ateneo Scientific Research (research projects 2017), both to MGB. FAC was recipient of a fellowship grant from the Associazione Medici Diabetologi (AMD) “Bando 5 per mille Fondazione AMD 2016”.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interests relevant to this study.

Ethical approval

The study was approved by the Ethical Committee of the University of Cagliari and conducted in conformance with the Helsinki Declaration.

Informed consent

Written consent was obtained from all the adult patients before the study. For children, written consent was obtained from the next of kin on behalf of the minors/children.

References

  1. 1.
    Assmann TS, Recamonde-Mendoza M, De Souza BM, Crispim D (2017) MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatics analysis. Endocr Connect 6:773–790CrossRefGoogle Scholar
  2. 2.
    Marchand L, Jalabert A, Meugnier E et al (2016) miRNA-375 a sensor of glucotoxicity is altered in the serum of children with newly diagnosed type 1 diabetes. J Diabetes Res 2016:1869082CrossRefGoogle Scholar
  3. 3.
    Zheng Y, Wang Z, Zhou Z (2017) miRNAs: novel regulators of autoimmunity-mediated pancreatic β-cell destruction in type 1 diabetes. Cell Mol Immunol 14:488–496CrossRefGoogle Scholar
  4. 4.
    Sims EK, Evans-Molina C, Tersey SA, Eizirik DL, Mirmira RG (2018) Biomarkers of islet beta cell stress and death in type 1 diabetes. Diabetologia 61:2259–2265CrossRefGoogle Scholar
  5. 5.
    Incani M, Serafini C, Satta C et al (2017) High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes. Diabetes Metab Res Rev 33(3):e2864CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endocrinology and Diabetes, Department of Experimental MedicineSapienza University of RomeRomeItaly
  2. 2.Department of Medical Sciences and Public HealthUniversity of CagliariCagliariItaly

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