MicroRNAs: potential regulators involved in human anencephaly.
MicroRNAs (miRNAs) are posttranscriptional regulators of messenger RNA activity. Neural tube defects (NTDs) are severe congenital anomalies that substantially impact an infant's morbidity and mortality. The miRNAs are known to be dynamically regulated during neurodevelopment; their role in human NTDs, however, is still unknown. In this study, we show the presence of a specific miRNA expression profile from tissues of fetuses with anencephaly, one of the most severe forms of NTDs. Furthermore, we map the target genes of these miRNAs in the human genome. In comparison to healthy human fetal brain tissues, tissues from fetuses with anencephaly exhibited 97 down-regulated and 116 up-regulated miRNAs. The microarray findings were extended using real-time qRT-PCR for nine miRNAs. Specifically, of these validated miRNAs, miR-126, miR-198, and miR-451 were up-regulated, while miR-9, miR-212, miR-124, miR-138, and miR-103/107 were down-regulated in the tissues of fetuses with anencephaly. A bioinformatic analysis showed 881 potential target genes that are regulated by the validated miRNAs. Seventy-nine of these potential genes are involved in a protein interaction network. There were 6 co-occurrence annotations within the GOSlim process and 7 co-occurrence annotations within the GOSlim function found by GeneCodis 2.0. Our results suggest that miRNA dysregulation is possibly involved in the pathogenesis of anencephaly.
Zhang
Zhiping
Z
Graduate School of Peking Union Medical College, Beijing, China. zzp754500@163.com
Chang
Huibo
H
Li
Yuanyuan
Y
Zhang
Ting
T
Zou
Jizhen
J
Zheng
Xiaoying
X
Wu
Jianxin
J
D000293:Adolescent; D000757:Anencephaly / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
D035683:MicroRNAs