Differentially expressed miRNAs in trisomy 21 placentas.
OBJECTIVE
Molecular pathogenesis of Down syndrome (DS) is still incompletely understood. Epigenetic mechanisms, including miRNAs gene expression regulation, belong to potential influencing factors. The aims of this study were to compare miRNAs expressions in placentas with normal and trisomic karyotype and to associate differentially expressed miRNAs with concrete biological pathways.


METHODS
A total of 80 CVS samples - 41 with trisomy 21 and 39 with normal karyotype - were included in our study. Results obtained in the pilot study using real-time PCR technology and TaqMan Human miRNA Array Cards were subsequently validated on different samples using individual TaqMan miRNA Assays.


RESULTS
Seven miRNAs were verified as upregulated in DS placentas (miR-99a, miR-542-5p, miR-10b, miR-125b, miR-615, let-7c and miR-654); three of these miRNAs are located on chromosome 21 (miR-99a, miR-125b and let-7c). Many essential biological processes, transcriptional regulation or apoptosis, were identified as being potentially influenced by altered miRNA levels. Moreover, miRNAs overexpressed in DS placenta apparently regulate genes involved in placenta development (GJA1, CDH11, EGF, ERVW-1, ERVFRD-1, LEP or INHA).


CONCLUSIONS
These findings suggest the possible participation of miRNAs in Down syndrome impaired placentation and connected pregnancy pathologies. © 2016 John Wiley & Sons, Ltd.
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Iveta
I
Svobodová
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Marie
M
Korabečná
Department of Obstetrics and Gynecology of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Pavel
http://orcid.org/0000-0002-2903-5026
P
Calda
Department of Obstetrics and Gynecology of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.|Screening Center ProfiG2, Prague, Czech Republic.
Miroslav
M
Břešťák
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Eva
E
Pazourková
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Šárka
Š
Pospíšilová
GENvia - Commercial Genetic Laboratories, Prague, Czech Republic.
Miroslava
M
Krkavcová
Department of Obstetrics and Gynecology of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Michaela
M
Novotná
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.|3rd Medical Department of Internal Medicine of the First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
Aleš
A
Hořínek
D000328:Adult; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D015193:Chorionic Villi Sampling; D018031:Connexin 43 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015686:Gene Products, env / Q000235:genetics; D006801:Humans; D007265:Inhibins / Q000235:genetics; D020738:Leptin / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010865:Pilot Projects; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation
D015820:Cadherins; D018031:Connexin 43; C518353:ERVFRD-1 protein, human; C500216:GJA1 protein, human; D015686:Gene Products, env; D020738:Leptin; C547183:MIRN10 microRNA, human; C531888:MIRN125 microRNA, human; C572357:MIRN542 microRNA, human; C534344:MIRN615 microRNA, human; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; D011257:Pregnancy Proteins; C094377:inhibin-alpha subunit; C487931:mirnlet7 microRNA, human; C405335:syncytin; C086960:osteoblast cadherin; D007265:Inhibins; D004815:Epidermal Growth Factor