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http://purl.uniprot.org/citations/27059371http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27059371http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.org/dc/terms/identifier"doi:10.1007/s00125-016-3945-0"xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Ellard S."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Patel K."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Hattersley A.T."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Malecki M.T."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Dobrzyn A."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Borowiec M."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Mlynarski W."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Mysliwiec M."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Szopa M."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Jarosz-Chobot P."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Fendler W."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Szadkowska A."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Janikiewicz J."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Madzio J."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Tracz A."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/author"Kozinski K."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/pages"1463-1473"xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/title"Differential regulation of serum microRNA expression by HNF1beta and HNF1alpha transcription factors."xsd:string
http://purl.uniprot.org/citations/27059371http://purl.uniprot.org/core/volume"59"xsd:string
http://purl.uniprot.org/citations/27059371http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27059371
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