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

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...

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Veröffentlicht in:Diabetologia 2016-07, Vol.59 (7), p.1463-1473
Hauptverfasser: 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 T., Ellard, Sian, Malecki, Maciej T., Dobrzyn, Agnieszka, Mlynarski, Wojciech
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Sprache:eng
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Zusammenfassung: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 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 HNF1α or HNF1β. Results Significant differences (adjusted p  
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-016-3945-0