Dataset Information

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

ABSTRACT:

Aims/hypothesis

We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1β 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 HbA1c-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 HNF1α or HNF1β.

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 HNF1α- than in HNF1β-deficient HepG2 cells.

Conclusions/interpretation

We have shown that expression of specific miRNAs depends on HNF1β function. The impact of HNF1β deficiency was evidenced at serum level, making HNF1β-dependent miRNAs potentially applicable in the diagnosis of HNF1B-MODY.

SUBMITTER: Fendler W

PROVIDER: S-EPMC4901123 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Fendler Wojciech W Madzio Joanna J Kozinski Kamil K Patel Kashyap K Janikiewicz Justyna J Szopa Magdalena M Tracz Adam A Borowiec Maciej M Jarosz-Chobot Przemyslawa P Mysliwiec Malgorzata M Szadkowska Agnieszka A Hattersley Andrew T AT Ellard Sian S Malecki Maciej T MT Dobrzyn Agnieszka A Mlynarski Wojciech W

Diabetologia 20160408 7

<h4>Aims/hypothesis</h4>We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1β transcription factor, and investigate whether its effect manifests in serum.<h4>Methods</h4>The Polish cohort (N = 60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 with GCK-MODY, an HbA1c-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 ...[more]

PMID: 27059371

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Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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

Similar Datasets

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