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Differential regulation of serum microRNA expression by HNF1β and HNF1α transcription factors

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00125-016-3945-0 Byline: Wojciech Fendler (1,2), Joanna Madzio (1,3), Kamil Kozinski (4), Kashyap Patel (5), Justyna Janikiewicz (4), Magdalena Szopa (6,7), Adam Tracz... Full description

Journal Title: Diabetologia 2016, Vol.59(7), pp.1463-1473
Main Author: Fendler, Wojciech
Other Authors: Madzio, Joanna , Kozinski, Kamil , Patel, Kashyap , Janikiewicz, Justyna , Szopa, Magdalena , Tracz, Adam , Borowiec, Maciej , Jarosz-Chobot, Przemyslawa , Mysliwiec, Malgorzata , Szadkowska, Agnieszka , Hattersley, Andrew , Ellard, Sian , Malecki, Maciej , Dobrzyn, Agnieszka , Mlynarski, Wojciech
Format: Electronic Article Electronic Article
Language: English
Subjects:
HNF
ID: ISSN: 0012-186X ; E-ISSN: 1432-0428 ; DOI: 10.1007/s00125-016-3945-0
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recordid: springer_jour10.1007/s00125-016-3945-0
title: Differential regulation of serum microRNA expression by HNF1β and HNF1α transcription factors
format: Article
creator:
  • Fendler, Wojciech
  • Madzio, Joanna
  • Kozinski, Kamil
  • Patel, Kashyap
  • Janikiewicz, Justyna
  • Szopa, Magdalena
  • Tracz, Adam
  • Borowiec, Maciej
  • Jarosz-Chobot, Przemyslawa
  • Mysliwiec, Malgorzata
  • Szadkowska, Agnieszka
  • Hattersley, Andrew
  • Ellard, Sian
  • Malecki, Maciej
  • Dobrzyn, Agnieszka
  • Mlynarski, Wojciech
subjects:
  • HNF
  • microRNA
  • MODY
  • Monogenic diabetes
  • Transcription factors
ispartof: Diabetologia, 2016, Vol.59(7), pp.1463-1473
description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00125-016-3945-0 Byline: Wojciech Fendler (1,2), Joanna Madzio (1,3), Kamil Kozinski (4), Kashyap Patel (5), Justyna Janikiewicz (4), Magdalena Szopa (6,7), Adam Tracz (1), Maciej Borowiec (8), Przemyslawa Jarosz-Chobot (9), Malgorzata Mysliwiec (10), Agnieszka Szadkowska (1), Andrew T. Hattersley (5), Sian Ellard (5), Maciej T. Malecki (6,7), Agnieszka Dobrzyn (4), Wojciech Mlynarski (1) Keywords: HNF; microRNA; MODY; Monogenic diabetes; Transcription factors Abstract: Aims/hypothesis We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1[beta] transcription factor, and investigate whether its effect manifests in serum. Methods The Polish cohort (N=60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 withGCK-MODY, an HbA.sub.1c-matched type 1 diabetic group (n=9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort. The Polish cohort underwent miRNA serum level profiling with quantitative real-time PCR (qPCR) arrays to identify differentially expressed miRNAs. Validation was performed using qPCR. To determine whether serum content reflects alterations at a cellular level, we quantified miRNA levels in a human hepatocyte cell line (HepG2) with small interfering RNA knockdowns of HNF1[alpha] or HNF1[beta]. Results Significant differences (adjusted p
language: eng
source:
identifier: ISSN: 0012-186X ; E-ISSN: 1432-0428 ; DOI: 10.1007/s00125-016-3945-0
fulltext: fulltext_linktorsrc
issn:
  • 1432-0428
  • 14320428
  • 0012-186X
  • 0012186X
url: Link


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titleDifferential regulation of serum microRNA expression by HNF1β and HNF1α transcription factors
creatorFendler, Wojciech ; Madzio, Joanna ; Kozinski, Kamil ; Patel, Kashyap ; Janikiewicz, Justyna ; Szopa, Magdalena ; Tracz, Adam ; Borowiec, Maciej ; Jarosz-Chobot, Przemyslawa ; Mysliwiec, Malgorzata ; Szadkowska, Agnieszka ; Hattersley, Andrew ; Ellard, Sian ; Malecki, Maciej ; Dobrzyn, Agnieszka ; Mlynarski, Wojciech
ispartofDiabetologia, 2016, Vol.59(7), pp.1463-1473
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subjectHNF ; microRNA ; MODY ; Monogenic diabetes ; Transcription factors
languageeng
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descriptionTo access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00125-016-3945-0 Byline: Wojciech Fendler (1,2), Joanna Madzio (1,3), Kamil Kozinski (4), Kashyap Patel (5), Justyna Janikiewicz (4), Magdalena Szopa (6,7), Adam Tracz (1), Maciej Borowiec (8), Przemyslawa Jarosz-Chobot (9), Malgorzata Mysliwiec (10), Agnieszka Szadkowska (1), Andrew T. Hattersley (5), Sian Ellard (5), Maciej T. Malecki (6,7), Agnieszka Dobrzyn (4), Wojciech Mlynarski (1) Keywords: HNF; microRNA; MODY; Monogenic diabetes; Transcription factors Abstract: Aims/hypothesis We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1[beta] transcription factor, and investigate whether its effect manifests in serum. Methods The Polish cohort (N=60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 withGCK-MODY, an HbA.sub.1c-matched type 1 diabetic group (n=9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort. The Polish cohort underwent miRNA serum level profiling with quantitative real-time PCR (qPCR) arrays to identify differentially expressed miRNAs. Validation was performed using qPCR. To determine whether serum content reflects alterations at a cellular level, we quantified miRNA levels in a human hepatocyte cell line (HepG2) with small interfering RNA knockdowns of HNF1[alpha] or HNF1[beta]. Results Significant differences (adjusted p<0.05) were noted for 11 miRNAs. Five of them differed between HNF1A-MODY and HNF1B-MODY, and, amongst those, four (miR-24, miR-27b, miR-223 and miR-199a) showed HNF1B-MODY-specific expression levels in the replication group. In all four cases the miRNA expression level was lower in HNF1B-MODY than in all other tested groups. Areas under the receiver operating characteristic curves ranged from 0.79 to 0.86, with sensitivity and specificity reaching 91.7% (miR-24) and 82.1% (miR-199a), respectively. The cellular expression pattern of miRNA was consistent with serum levels, as all were significantly higher in HNF1[alpha]- than in HNF1[beta]-deficient HepG2 cells. Conclusions/interpretation We have shown that expression of specific miRNAs depends on HNF1[beta] function. The impact of HNF1[beta] deficiency was evidenced at serum level, making HNF1[beta]-dependent miRNAs potentially applicable in the diagnosis of HNF1B-MODY. Author Affiliation: (1) Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz, Lodz, Poland (2) Department of Biostatistics and Translational Medicine, Medical University of Lodz, 36/50 Sporna Str., 91-738, Lodz, Poland (3) Studies in Molecular Medicine, Medical University of Warsaw, Warsaw, Poland (4) Laboratory of Cell Signalling and Metabolic Disorders, Nencki Institute of Experimental Medicine, Polish Academy of Sciences, Warsaw, Poland (5) Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK (6) Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland (7) University Hospital, Krakow, Poland (8) Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland (9) Department of Paediatric Diabetology, Medical University of Silesia, Katowice, Poland (10) Department of Paediatrics, Diabetology and Endocrinology, Medical University of Gdansk, Gdansk, Poland Article History: Registration Date: 23/03/2016 Received Date: 31/12/2015 Accepted Date: 10/03/2016 Online Date: 08/04/2016 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00125-016-3945-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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