MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21.
OBJECTIVE
The objective of this study was to discover a panel of microRNAs (miRNAs) as potential biomarkers for noninvasive prenatal testing (NIPT) of trisomy 21 (T21) and to predict the biological functions of identified biomarkers using bioinformatics tools.


METHODS
Using microarray-based genome-wide expression profiling, we compared the expression levels of miRNAs in whole blood samples from non-pregnant women, whole blood samples from pregnant women with euploid or T21 fetuses, and placenta samples from euploid or T21 fetuses. We analyzed the differentially expressed miRNAs according to disease and tissue type (P value <0.05 and two-fold expression change). To predict functions of target genes of miRNAs, the functional annotation tools were used.


RESULTS
We identified 299 miRNAs which reasonably separate the whole blood from the placenta. Among the identified miRNAs, 150 miRNAs were up-regulated in the placenta, and 149 miRNAs were down-regulated. Most of the up-regulated miRNAs in the placenta were members of the mir-498, mir-379, and mir-127 clusters. Among the up-regulated miRNAs in the placenta, mir-1973 and mir-3196 were expressed at higher levels in the T21 placenta than in the euploid placenta. The two miRNAs potentially regulate 203 target genes that are involved in development of brain, central nervous system, and nervous system. The genes are significantly associated with T21-related disorder such as congenital abnormalities, mental disorders, and nervous system diseases.


CONCLUSIONS
Our study indicates placenta-specific miRNAs that may be potential biomarkers for NIPT of fetal T21 and provides new insights into the molecular mechanisms of T21 via regulation of miRNAs.
Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
Ji Hyae
JH
Lim
Da Eun
DE
Lee
Shin Young
SY
Kim
Hyun Jin
HJ
Kim
Kyeong Sun
KS
Kim
You Jung
YJ
Han
Min Hyoung
MH
Kim
Jun Seek
JS
Choi
Moon Young
MY
Kim
Hyun Mee
HM
Ryu
So Yeon
SY
Park
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D019295:Computational Biology; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011379:Prognosis
D015415:Biomarkers; D035683:MicroRNAs