Abstract
BackgroundsDown syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidies. The main characteristic of DS patients is intellectual disability. MicroRNAs (miRNAs) play important regulatory roles in various biological processes, such as embryonic development, cell differentiation, proliferation and apoptosis. Several miRNAs have shown association with DS. However, the role of miRNAs in DS patients has not been well elaborated.MethodsIn this research, total RNA extracted from fetal hippocampal tissues was used to analyze miRNA and mRNA expression via Affymetrix miRNA 4.0 and PrimeView Human Gene Expression Array, respectively. Then miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their predicted target mRNAs. Microarray data were further validated by real-time PCR. Regulation of zeste homolog 2 (EZH2) expression by hsa-miR-138 was determined by luciferase reporter assay.ResultsWe analyzed microRNA expression profile in hippocampal tissues from DS fetal using miRNA microarray. Further with the use of mRNA microarray data, we integrate miRNA expression and mRNA expression in hippocampus of trisomy 21 fetus to elucidate the mechanism that underlying DS abnormalities. We characterized the repertoire of specific miRNAs involved in hippocampus in trisomy 21 patients, highlighting hsa-miR-138 and hsa-miR-409, in particular the importance of hsa-miR-138, especially the -5p strand. Furthermore, the expression level of predicted target genes of hsa-miR-138-5p in trisomy 21 fetus, including zeste homolog 2 (EZH2) were further confirmed. In addition, luciferase assay indicated that EZH2 was a direct target of hsa-miR-138 in HEK293T cells.ConclusionThe function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-016-0265-0) contains supplementary material, which is available to authorized users.
Highlights
Down syndrome (DS), or trisomy 21 [MIM: 190685], is a common chromosomal abnormality
The function of hsa-miR-138-5p and its target enhancer of zeste homolog 2 (EZH2) was involved in hippocampus in DS patients
Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients
Summary
Down syndrome (DS), or trisomy 21 [MIM: 190685], is a common chromosomal abnormality. This disease is caused by an extra copy of chromosomal 21 and called trisomy. There are various phenotypes in DS population, including craniofacial abnormality, learning disabilities, congenital heart disease, leukemia’s, Alzheimer’s disease and a variety of physical features such as slanted eye, abnormal pattern of fingerprint, large tongue [2, 3]. The main neurological deficiency in DS patients is intellectual disability and early onset of Alzheimer’s disease [4]. The role of miRNA in intellectual disability of DS patients is largely unknown. Elucidation of neurological deficiency in DS patients will contribute to better understand of this disease
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