Identification of Potential miRNA-mRNA Regulatory Network in Tetralogy of Fallot: A Network Biology Approach

Abstract

BackgroundTetralogy of Fallot (ToF) is one of the most prevalent and fatal birth defects. Its pathogenesis remains unknown and it’s not easily diagnosed at early stage. Therefore, it’s necessary to explore the critical regulators and molecular mechanism in ToF to find out novel molecular markers for early diagnosis.MethodsThree ToF datasets (GSE35490, GSE40128, GSE36761) were downloaded from the GEO database. The differentially expressed microRNAs (DEMs) and mRNAs (DEGs) were identified between ToF infants and normal infants after data preprocessing, followed by GO and KEGG analysis of DEGs. Then, PPI network and modular analysis were performed to identify the hub genes. Ultimately, potential miRNA-mRNA pathways in ToF were constructed based on the integrated data.Results22 overlapping DEMs were found in the GES35490 and GSE40128. Simultaneous, 181 intersected genes were found and identified as the significant DEGs including 84 down-regulated DEGs and 97 up-regulated DEGs. Further, 20 hub genes ranked by top 10% with high connectivity, including STAT3, FBN1, RUNX2, were found by PPT network and modular analysis. Furthermore, GO and KEGG analysis showed these DEGs were linked to cell cycle, apoptotic process, transcription activity and FOX signaling pathway. Additionally, we establish three potential miRNA-mRNA pathway, including miR-22-STAT3, miR-336/miR486-FBN1, miR-222-RUNX2, which can participate in the formation of ToF by cell cycle and transcription activity.ConclusionsThree miRNA-mRNA pathways were established and indicated cell cycle and transcription activity may be involved in the pathogenesis of ToF. Our study provided a novel bio-marker for early diagnosis of ToF.