Circulating miRNA-375 levels are increased in autoantibodies-positive first-degree relatives of type 1 diabetes patients
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) .
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 . Recent studies have demonstrated that miRNAs are detected not only inside cells but also in extracellular fluids and body secretions . 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 . 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 .
KeywordsMicroRNAs Autoantibodies c-Peptide Sardinia Beta-cells Autoimmunity
Area under the curve
Acid decarboxylase autoantibodies
Tyrosine phosphatase autoantibodies
Impaired glucose regulation
Receiver operating characteristic
Type 1 diabetes
Zinc transporter 8 autoantobodies
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).
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.
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.
The study was approved by the Ethical Committee of the University of Cagliari and conducted in conformance with the Helsinki Declaration.
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.