Abstract
BackgroundThe most frequent chromosomal aneuploidy is trisomy 21 (T21) that is caused by an extra copy of chromosome 21. The imbalance of whole genome including genes and microRNAs contributes to the various phenotypes of T21. However, the integrative association between genes and microRNAs in the T21 placenta has yet to be determined.MethodsWe analyzed the expressions of genes and microRNAs in the whole genomes of chorionic villi cells from normal and T21 human fetal placentas based on our prior studies. The functional significances and interactions of the genes and microRNAs were predicted using bioinformatics tools.ResultsAmong 110 genes and 34 microRNAs showing significantly differential expression between the T21 and normal placentas, the expression levels of 17 genes were negatively correlated with those of eight microRNAs in the T21 group. Of these 17 genes, 10 with decreased expression were targeted by five up-regulated microRNAs, whereas seven genes with increased expression were targeted by three down-regulated microRNAs. These genes were significantly associated with hydrogen peroxide-mediated programmed cell death, cell chemotaxis, and protein self-association. They were also associated with T21 and its accompanying abnormalities. The constructed interactive signaling network showed that seven genes (three increased and four decreased expressions) were essential components of a dynamic signaling complex (P = 7.77e-16).ConclusionsIn this study, we have described the interplay of genes and microRNAs in the T21 placentas and their modulation in biological pathways related to T21 pathogenesis. These results may therefore contribute to further research about the interaction of genes and microRNAs in disease pathogenesis.
Highlights
The most frequent chromosomal aneuploidy is trisomy 21 (T21) that is caused by an extra copy of chromosome 21
Our results demonstrated that 34 miRNAs (16 up-regulated and 18 down-regulated) and 110 genes (77 up-regulated and 33 down-regulated) were significantly differentially expressed in the T21 placenta compared with that in normal placentas
The chorionic villi sampling (CVS) from five euploid and three T21 placentas were used for expression profiling of genome-wide whole genes [20], and those from the other five euploid and four T21 placentas were used for miRNA expression analysis [21]
Summary
The most frequent chromosomal aneuploidy is trisomy 21 (T21) that is caused by an extra copy of chromosome 21. Individuals with T21 have an increased risk of various congenital abnormalities, including eye, cardiac, gastrointestinal, renal and urinary tract defects [2]. These defects are generally considered to originate from gene dosage imbalance between the trisomic genes on chromosome 21 and the MicroRNAs (miRNAs) are small (18~ 25-nucleotidelong) non-coding endogenous RNAs. These defects are generally considered to originate from gene dosage imbalance between the trisomic genes on chromosome 21 and the MicroRNAs (miRNAs) are small (18~ 25-nucleotidelong) non-coding endogenous RNAs They regulate expression of genes at the post-transcriptional level by regulating mRNA stability and translation [6,7,8,9].
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