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MicroRNAs Profiling and Functional Study in Anencephaly

Author: YuXiao
Tutor: LuoXiaoPing
School: Huazhong University of Science and Technology
Course: Pediatrics
Keywords: anencephaly neural tube defects microRNA bioinformatics microarray cell transfection microRNA mimics Notch1 gene Dll1 gene
CLC: R714.5
Type: PhD thesis
Year: 2011
Downloads: 16
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Background: Neural tube defects (NTDs) is one of the most common congenital abnormalities in humans, occurring in 1 per 1000 live births. One of the most common NTDs is anencephaly. Multiple factors have been implicated in the etiology of NTDs, including genetic and environmental. microRNAs are small non-coding transcripts. Recently, miRNAs have been considered as a driving force in embryonic neurogenesis. Some specific miRNAs and target genes may explain the etiology of NTDs.Objective: To investigate the globle expression profiling of microRNAs in brain tissues of fetuses with anencephaly and normal control by using microRNA microarray, and predict the target genes of some specific miRNAs with bioinformatic method.Methods: The profiling of miRNAs from brain tissues of 3 fetuses with anencephaly and normal brains was detected using an Affymetrix GeneChip? miRNA microarray. Then some of the significantly misexpressed miRNAs were selected to validate the microarray assay results by real-time RT-PCR analysis. Furthermore, the target genes of these miRNAs were predicted with some online databases.Results: 1. Compared to the normal group, anencephaly group has a specific miRNA expression profile. There were 73 up-regulated miRNAs and 14 down-regulated miRNAs. 2. The microarray findings were extended using Real-time RT-PCR for 10 miRNAs. Of these miRNAs validated, mir-103, mir-132, mir-138, mir-185, mir-23a, mir-134, mir-22 and mir-34a were up-regulated, whereas mir-149 was down-regulated in the tissues from fetuses with anencephaly. In addition, mir-125a was found to be higher in anencephaly group than in the normal group, which contradicted the result detected by the microarray. Conclusion: This study shows that brain tissues of anencephaly group have a significantly misexpressed miRNA expression profile compared to that of normal group. And these misexpressed miRNAs may involve in the pathogenesis of NTDs. Background: A lot of previous studies showed that some specific miRNAs may have effect on folate metabolism and NTDs. In these miRNAs, mir-34a which has most obvious effects is chosen for further study. Notch1 and Dll1 may be regulated by mir-34a according to microRNA target prediction and functional study database. A number of studies suggest that notch signaling pathway may play a key role during fetal neurogenesis. So we speculate that miRNAs may influence neurogenesis process by regulating some important signaling pathway.Objective: To investigate the effect of mir-34a on Notch signaling pathway in human glioma cells lines U87.Method: Human glioma cells lines U87 was transfected with mir-34a mimics by lipofectamine 2000. After 24h, Real-time RT-PCR technology was used to detected change of mir-34a, Notch1 and Dll1 mRNA, and Western blot was used to detected change of Notch1 and Dll1 protein.Results: The mRNA level of mir-34a in U87 was obviously up-regulated. No significant change was detected in the mRNA expression of Notch1 and Dll1 in U87 cell line. However, the protein level of two genes significantly decreased after mir-34a was up-regulated.Conclusion: It indicates that miRNAs inhibit expression of target genes on transcription level. And mir-34a may impact on the signaling pathways of pathogenesis of NTDs by prevent the translation of Notch1.

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CLC: > Medicine, health > Obstetrics and Gynaecology > Obstetrics > Fetus
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