【摘 要】
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Background Tetralogy of Fallot (TOF) is one of the most common heart defects in children and the underlying mechanisms remain elusive.miRNAs are a recently discovered class of regulators of gene expre
【机 构】
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Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecula
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Background Tetralogy of Fallot (TOF) is one of the most common heart defects in children and the underlying mechanisms remain elusive.miRNAs are a recently discovered class of regulators of gene expression and are becoming increasingly recognized as important regulators of heart development and function.Methods and results To identify miRNAs abnormally expressed in clinical heart tissues of TOFs, microarray was used to analyze miRNA expression profiles in 5 myectomy tissues from right ventricular outflow tract (RVOT) obstruction of infants with non-syndromic TOF and 3 age-matched normal RVOT tissues, and 41 candidate miRNAs were identified.To further validate the results of miRNA microarrays, the 41 candidate miRNAs were re-detected in 26 RVOT myocardium samples form TOF and 6 age-matched normal controls by real-time RT-PCR and 23 miRNAs showed significantly different expression in TOF tissues compared to normal ones.Bioinformatic analysis showed that they targeted a network of genes involved in heart development and human congenital heart diseases.Further in vitro studies showed that up-regulation of miR-424/424* promoted proliferation and inhibited migration of primary embryonic mouse cardiomyocyte, while miR-222 promoted cardiomyocyte proliferation and reduced cardiomyogenic differentiation of P19 cells.3-UTR luciferase assay revealed that miR-424/424* suppressed expression of HAS2 and NF1, and they were underexpressed in RVOT myocardium tissues of TOFs compared with the normal ones.Conclusion Our research identified 23 miRNAs deregulated in RVOT myocardium tissues from infants with non-syndromic TOF, and that miR-424/424* and miR-222 were involved in cardiomyocyte proliferation and migration, and cardiomyogenicdifferentiation of P19 cells.
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