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PLoS One. 2014 Aug 28;9(8):e106318. doi: 10.1371/journal.pone.0106318. eCollection 2014.

Characterization of circulating microRNA expression in patients with a ventricular septal defect.

Author information

1
Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, Shandong Province, China; School of Public Health, Taishan Medical University, Tai'an, Shandong Province, China.
2
School of Public Health, Taishan Medical University, Tai'an, Shandong Province, China.
3
Tai'an Children's Hospital, Tai'an, Shandong Province, China.
4
Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, Shandong Province, China.

Abstract

OBJECTIVES:

Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD.

METHODS:

MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods.

RESULTS:

36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433.

CONCLUSION:

We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

PMID:
25165856
PMCID:
PMC4148428
DOI:
10.1371/journal.pone.0106318
[Indexed for MEDLINE]
Free PMC Article

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