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Differential regulation of serum microRNA expression by
HNF
microRNA
MODY
monogenic diabetes
transcription factors
We aimed to identify microRNAs (miRNAs) under transcriptional control of the
cris.lastimport.scopus | 2024-04-07T17:33:06Z | |
dc.abstract.en | 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. | pl |
dc.affiliation | Wydział Lekarski : Zakład Dydaktyki Medycznej | pl |
dc.affiliation | Wydział Lekarski : Klinika Chorób Metabolicznych | pl |
dc.cm.date | 2020-01-07 | |
dc.cm.id | 77907 | |
dc.contributor.author | Fendler, Wojciech | pl |
dc.contributor.author | Madzio, Joanna | pl |
dc.contributor.author | Kozinski, Kamil | pl |
dc.contributor.author | Patel, Kashyap | pl |
dc.contributor.author | Janikiewicz, Justyna | pl |
dc.contributor.author | Szopa, Magdalena - 133593 | pl |
dc.contributor.author | Tracz, Adam | pl |
dc.contributor.author | Borowiec, Maciej | pl |
dc.contributor.author | Jarosz-Chobot, Przemysława | pl |
dc.contributor.author | Myśliwiec, Małgorzata | pl |
dc.contributor.author | Szadkowska, Agnieszka | pl |
dc.contributor.author | Hattersley, Andrew T. | pl |
dc.contributor.author | Ellard, Sian | pl |
dc.contributor.author | Małecki, Maciej - 130840 | pl |
dc.contributor.author | Dobrzyn, Agnieszka | pl |
dc.contributor.author | Młynarski, Wojciech Michał | pl |
dc.date.accessioned | 2020-01-17T09:04:08Z | |
dc.date.available | 2020-01-17T09:04:08Z | |
dc.date.issued | 2016 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.number | 7 | pl |
dc.description.physical | 1463-1473 | pl |
dc.description.points | 40 | pl |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 59 | pl |
dc.identifier.doi | 10.1007/s00125-016-3945-0 | pl |
dc.identifier.eissn | 1432-0428 | pl |
dc.identifier.issn | 0012-186X | pl |
dc.identifier.project | ROD UJ / OP | pl |
dc.identifier.uri | https://ruj.uj.edu.pl/xmlui/handle/item/137952 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | * |
dc.rights.licence | CC-BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | * |
dc.share.type | inne | |
dc.subject.en | HNF | pl |
dc.subject.en | microRNA | pl |
dc.subject.en | MODY | pl |
dc.subject.en | monogenic diabetes | pl |
dc.subject.en | transcription factors | pl |
dc.subtype | Article | pl |
dc.title | Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors | pl |
dc.title.journal | Diabetologia | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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