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Sexual difference of small RNA expression in Tetralogy of Fallot.

ABSTRACT: Small RNAs, especially the microRNAs, have been revealed to play great roles in heart development and congenital heart defects. Several studies have shown dysregulated miRNAs in ventricular tissues of Tetralogy of Fallot (TOF) patients. In the present study, we conducted high throughput sequencing to obtain the global profiling of small RNA transcriptome in heart right ventricular samples from 10 age -matched TOF patients. These samples showed dominant composition of miRNA and mitochondrial associated RNAs. By sRNA cluster identification and differential gene expression analysis, significant sexual difference was discovered for sRNA expression in TOF patients. miR-1/miR-133, which have been identified as essential for cardiac development, account for the most variance of sRNA expression between sexes in TOF hearts.

SUBMITTER: Wang B

PROVIDER: S-EPMC6110777 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Sexual difference of small RNA expression in Tetralogy of Fallot.

Wang Bo B Shi Guocheng G Zhu Zhongqun Z Chen Huiwen H Fu Qihua Q

Scientific reports 20180827 1

Small RNAs, especially the microRNAs, have been revealed to play great roles in heart development and congenital heart defects. Several studies have shown dysregulated miRNAs in ventricular tissues of Tetralogy of Fallot (TOF) patients. In the present study, we conducted high throughput sequencing to obtain the global profiling of small RNA transcriptome in heart right ventricular samples from 10 age -matched TOF patients. These samples showed dominant composition of miRNA and mitochondrial asso ...[more]

PMID: 30150777

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Sexual difference of small RNA expression in Tetralogy of Fallot

Project description:Small RNAs, especially the microRNAs, have been revealed to play great roles in heart development and congenital heart defects. Several studies have shown dysregulated miRNAs in ventricular tissues of Tetralogy of Fallot (TOF) patients. In the present study, we conducted high throughput sequencing to obtain the global profiling of small RNA transcriptome in heart right ventricular samples from 10 age -matched TOF patients. These samples showed dominant composition of miRNA and mitochondrial associated RNAs. By sRNA cluster identification and differential gene expression analysis, significant sexual difference was discovered for sRNA expression in TOF patients. miR-1/miR-133, the first identified miRNA cluster essential for cardiac development, account for the most variance of sRNA expression between sexes. Our results suggested divergent molecular basis between female and male TOF patients.

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Project description:MicroRNAs (miRNAs) play an important role in guiding development and maintaining function of the human heart. Dysregulation of miRNAs has been linked to various congenital heart diseases including Tetralogy of Fallot (TOF), which represents the most common cyanotic heart malformation in humans. Several studies have identified dysregulated miRNAs in right ventricular (RV) tissues of TOF patients. In this study, we profiled genome-wide the whole transcriptome and analyzed the relationship of miRNAs and mRNAs of RV tissues of a homogeneous group of 22 non-syndromic TOF patients. Observed profiles were compared to profiles obtained from right and left ventricular tissue of normal hearts. To reduce the commonly observed large list of predicted target genes of dysregulated miRNAs, we applied a stringent target prediction pipeline integrating probabilities for miRNA-mRNA interaction. The final list of disease-related miRNA-mRNA pairs comprises novel as well as known miRNAs including miR-1 and miR-133, which are essential to cardiac development and function by regulating KCNJ2, FBN2, SLC38A3 and TNNI1. Overall, our study provides additional insights into post-transcriptional gene regulation of malformed hearts of TOF patients.

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Noncoding RNA expression in myocardium from infants with tetralogy of Fallot

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Noncoding RNA expression in myocardium from infants with tetralogy of Fallot

Project description:This SuperSeries is composed of the SubSeries listed below.

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MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot.

Project description:The importance of microRNAs for maintaining stability in the developing vertebrate heart has recently become apparent. In addition, there is a growing appreciation for the significance of microRNAs in developmental pathology, including the formation of congenital heart defects. We examined the expression of microRNAs in right ventricular (RV) myocardium from infants with idiopathic tetralogy of Fallot (TOF, without a 22q11.2 deletion), and found 61 microRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects (O'Brien et al. 2012). Predicted targets of microRNAs with altered expression were enriched for gene networks that regulate cardiac development. We previously derived a list of 229 genes known to be critical to heart development, and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlations with 33 microRNAs, each of which also had significantly changed expression. Here, we focus on miR-421, as it is significantly upregulated in RV tissue from infants with TOF; is predicted to interact with multiple members of cardiovascular regulatory pathways; and has been shown to regulate cell proliferation. We knocked down, and over expressed miR-421 in primary cells derived from the RV of infants with TOF, and infants with normally developing hearts, respectively. We found a significant inverse correlation between the expression of miR-421 and SOX4, a key regulator of the Notch pathway, which has been shown to be important for the cardiac outflow track. These findings suggest that the dysregulation of miR-421 warrants further investigation as a potential contributor to tetralogy of Fallot.

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