Affiliation:
1. Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, Xuzhou, Xuzhou, Jiangsu, China
Abstract
Background:
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart
disease in clinical practice. It is mainly due to cardiovascular hypoplasia during embryonic development.
The study aimed to find the etiology of TOF.
Method:
Through the mRNA expression profile analysis of the GSE35776 dataset, differentially
expressed genes (DEGs) were found, and the functional analysis and protein-protein interaction
(PPI) network analysis were then performed on DEGs. Likewise, the hub genes and functional
clusters of DEGs were analyzed using the PPI network. Differentially expressed miRNAs were analyzed
from the GSE35490 dataset, followed by miRNet predicted transcription factors (TFs) and
target genes. The key TF-miRNA-gene interaction mechanism was explored through the found
significant difference between genes and target genes.
Results:
A total of 191 differentially expressed genes and 57 differentially expressed miRNAs
were identified. The main mechanisms involved in TOF were mitochondria-related and energy metabolism-
related molecules and pathways in GO and KEGG analysis. This discovery was identical
in TFs and target genes. The key miRNAs, hsa-mir-16 and hsa-mir-124, were discovered by the
Venn diagram. A co-expression network with the mechanism of action centered on two miRNAs
was made.
Conclusion:
Hsa-mir-16 and hsa-mir-124 are the key miRNAs of TOF, which mainly regulate the
expression of NT5DC1, ECHDC1, HSDL2, FCHO2, and ACAA2 involved in the conversion of
ATP in the mitochondria and the metabolic rate of fatty acids (FA). Our research provides key
molecules and pathways into the etiology of TOF, which can be used as therapeutic targets.
Funder
National Natural Science Foundation of China
Natural Science Research of Jiangsu Higher Education Institutions of China
Scientific Research Projects for Outstanding Teachers of Xuzhou Medical University
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine
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