Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors

doi:10.1007/s00125-016-3945-0

Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors

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Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors

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punktacja MEiN [2016 A]: 40

title:	Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors
author:	Fendler Wojciech, Madzio Joanna, Kozinski Kamil, Patel Kashyap, Janikiewicz Justyna, Szopa Magdalena , Tracz Adam, Borowiec Maciej, Jarosz-Chobot Przemysława, Myśliwiec Małgorzata, Szadkowska Agnieszka, Hattersley Andrew T., Ellard Sian, Małecki Maciej , Dobrzyn Agnieszka, Młynarski Wojciech Michał
journal title:	Diabetologia
volume:	59
issue:	7
date of publication :	2016
pages:	1463-1473
ISSN:	0012-186X
eISSN:	1432-0428
DOI:	10.1007/s00125-016-3945-0
language:	English
journal language:	English
abstract in English:	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 with GCK-MODY, an $HbA _{1c}$-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.
keywords in English:	HNF, microRNA, MODY, monogenic diabetes, transcription factors
departmental parameterization:	40
affiliation:	Wydział Lekarski : Zakład Dydaktyki Medycznej, Wydział Lekarski : Klinika Chorób Metabolicznych
type:	journal article
subtype:	academic paper