Differential regulation of serum microRNA expression by and transcription factors

2016
journal article
article
18
dc.abstract.enWe 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.affiliationWydział Lekarski : Zakład Dydaktyki Medycznejpl
dc.affiliationWydział Lekarski : Klinika Chorób Metabolicznychpl
dc.cm.date2020-01-07
dc.cm.id77907
dc.contributor.authorFendler, Wojciechpl
dc.contributor.authorMadzio, Joannapl
dc.contributor.authorKozinski, Kamilpl
dc.contributor.authorPatel, Kashyappl
dc.contributor.authorJanikiewicz, Justynapl
dc.contributor.authorSzopa, Magdalena - 133593 pl
dc.contributor.authorTracz, Adampl
dc.contributor.authorBorowiec, Maciejpl
dc.contributor.authorJarosz-Chobot, Przemysławapl
dc.contributor.authorMyśliwiec, Małgorzatapl
dc.contributor.authorSzadkowska, Agnieszkapl
dc.contributor.authorHattersley, Andrew T.pl
dc.contributor.authorEllard, Sianpl
dc.contributor.authorMałecki, Maciej - 130840 pl
dc.contributor.authorDobrzyn, Agnieszkapl
dc.contributor.authorMłynarski, Wojciech Michałpl
dc.date.accessioned2020-01-17T09:04:08Z
dc.date.available2020-01-17T09:04:08Z
dc.date.issued2016pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number7pl
dc.description.physical1463-1473pl
dc.description.points40pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume59pl
dc.identifier.doi10.1007/s00125-016-3945-0pl
dc.identifier.eissn1432-0428pl
dc.identifier.issn0012-186Xpl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/137952
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enHNFpl
dc.subject.enmicroRNApl
dc.subject.enMODYpl
dc.subject.enmonogenic diabetespl
dc.subject.entranscription factorspl
dc.subtypeArticlepl
dc.titleDifferential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factorspl
dc.title.journalDiabetologiapl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
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.
dc.affiliationpl
Wydział Lekarski : Zakład Dydaktyki Medycznej
dc.affiliationpl
Wydział Lekarski : Klinika Chorób Metabolicznych
dc.cm.date
2020-01-07
dc.cm.id
77907
dc.contributor.authorpl
Fendler, Wojciech
dc.contributor.authorpl
Madzio, Joanna
dc.contributor.authorpl
Kozinski, Kamil
dc.contributor.authorpl
Patel, Kashyap
dc.contributor.authorpl
Janikiewicz, Justyna
dc.contributor.authorpl
Szopa, Magdalena - 133593
dc.contributor.authorpl
Tracz, Adam
dc.contributor.authorpl
Borowiec, Maciej
dc.contributor.authorpl
Jarosz-Chobot, Przemysława
dc.contributor.authorpl
Myśliwiec, Małgorzata
dc.contributor.authorpl
Szadkowska, Agnieszka
dc.contributor.authorpl
Hattersley, Andrew T.
dc.contributor.authorpl
Ellard, Sian
dc.contributor.authorpl
Małecki, Maciej - 130840
dc.contributor.authorpl
Dobrzyn, Agnieszka
dc.contributor.authorpl
Młynarski, Wojciech Michał
dc.date.accessioned
2020-01-17T09:04:08Z
dc.date.available
2020-01-17T09:04:08Z
dc.date.issuedpl
2016
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
7
dc.description.physicalpl
1463-1473
dc.description.pointspl
40
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
59
dc.identifier.doipl
10.1007/s00125-016-3945-0
dc.identifier.eissnpl
1432-0428
dc.identifier.issnpl
0012-186X
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/137952
dc.languagepl
eng
dc.language.containerpl
eng
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.enpl
HNF
dc.subject.enpl
microRNA
dc.subject.enpl
MODY
dc.subject.enpl
monogenic diabetes
dc.subject.enpl
transcription factors
dc.subtypepl
Article
dc.titlepl
Differential regulation of serum microRNA expression by $HNF1\beta$ and $HNF1\alpha$ transcription factors
dc.title.journalpl
Diabetologia
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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