Magdalena Zurawek1, Agnieszka Dzikiewicz-Krawczyk2, Katarzyna Izykowska2, Iwona Ziolkowska-Suchanek2, Bogda Skowronska3, Maria Czainska4, Marta Podralska2, Piotr Fichna3, Grzegorz Przybylski2, Marta Fichna5, Jerzy Nowak2. 1. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address: magdalena.zurawek@igcz.poznan.pl. 2. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. 3. Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poznan, Poland. 4. Family Physician Clinic, Murowana Goslina, Poland. 5. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Department of Endocrinology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
Abstract
AIMS: Type 1 diabetes (T1D) is an autoimmune disorder caused by the T-cell mediated destruction of the insulin-producing pancreatic beta cells. T1D is a consequence of complex processes, influenced by genetic, epigenetic and environmental factors. MicroRNAs (miRNAs) are small non-coding RNAs that target multiple mRNAs and regulate gene expression. The implication of miRNAs in T1D pathogenesis, as potential modulators of immune response genes, remains poorly defined. The aim of this study was to investigate the expression profile of miRNAs in new onset T1D and the impact of deregulated miRNAs on target genes. METHODS: Total RNA from peripheral blood mononuclear cells of newly diagnosed T1D pediatric patients and age-matched controls was screened for disease-associated miRNAs by a microarray analysis, with subsequent validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). miRNA targets were identified by luciferase reporter assays. RESULTS: The microarray analysis revealed 91 deregulated miRNAs (P < 0.05) in T1D group compared to non-diabetic controls. Within this group we observed one upregulated and seven downregulated miRNAs with fold change >2.0. qRT-PCR validation revealed overexpression of miR-487a-3p which has not been previously reported in the context of T1D. Luciferase reporter assays indicated CTLA4 and FOXO3 genes as miR-487a-3p targets. CONCLUSION: Our study suggests that miR-487a-3p might repress CTLA4 and FOXO3 by binding to their 3'UTRs and contribute to the development of T1D.
AIMS: Type 1 diabetes (T1D) is an autoimmune disorder caused by the T-cell mediated destruction of the insulin-producing pancreatic beta cells. T1D is a consequence of complex processes, influenced by genetic, epigenetic and environmental factors. MicroRNAs (miRNAs) are small non-coding RNAs that target multiple mRNAs and regulate gene expression. The implication of miRNAs in T1D pathogenesis, as potential modulators of immune response genes, remains poorly defined. The aim of this study was to investigate the expression profile of miRNAs in new onset T1D and the impact of deregulated miRNAs on target genes. METHODS: Total RNA from peripheral blood mononuclear cells of newly diagnosed T1D pediatric patients and age-matched controls was screened for disease-associated miRNAs by a microarray analysis, with subsequent validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). miRNA targets were identified by luciferase reporter assays. RESULTS: The microarray analysis revealed 91 deregulated miRNAs (P < 0.05) in T1D group compared to non-diabetic controls. Within this group we observed one upregulated and seven downregulated miRNAs with fold change >2.0. qRT-PCR validation revealed overexpression of miR-487a-3p which has not been previously reported in the context of T1D. Luciferase reporter assays indicated CTLA4 and FOXO3 genes as miR-487a-3p targets. CONCLUSION: Our study suggests that miR-487a-3p might repress CTLA4 and FOXO3 by binding to their 3'UTRs and contribute to the development of T1D.
Authors: Tana Machackova; Karolina Trachtova; Vladimir Prochazka; Tomas Grolich; Martina Farkasova; Lukas Fiala; Roman Sefr; Igor Kiss; Matej Skrovina; Michal Dosoudil; Ioana Berindan-Neagoe; Marek Svoboda; Ondrej Slaby; Zdenek Kala Journal: Cancer Genomics Proteomics Date: 2020 May-Jun Impact factor: 4.069
Authors: Magdalena Zurawek; Marta Fichna; Piotr Fichna; Maria Czainska; Natalia Rozwadowska Journal: J Immunol Res Date: 2020-08-12 Impact factor: 4.818