Systematic large-scale meta-analysis identifies miRNA-429/200a/b and miRNA-141/200c clusters as biomarkers for necrotizing enterocolitis in newborn

Abstract

Necrotizing enterocolitis (NEC) is a critical neonatal disease with a high mortality. The possibility that miRNAs may play an important role in NEC has raised great attention. Hence, the present study identified biomarkers that affected NEC in newborn progression through miRNA and gene expression profile analysis. miRNA chip GSE68054 and gene chip GSE46619 of NEC in newborn were analyzed to screen out differentially expressed miRNA and differentially expressed genes (DEGs). Next, target genes of differentially expressed miRNA were predicted, and differentially expressed miRNA-DEG regulatory network was constructed to select key miRNAs. After gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis on target genes of key miRNAs, the target genes enriched in pathways were extracted to establish differentially expressed miRNA-DEG-disease gene network for gene interaction analysis. Targetting relationship between miRNAs and target genes was verified. A total of 15 miRNAs were differentially expressed in NEC in newborn, amongst which miR-429/200a/b and miR-141/200c clusters were poorly expressed and might play a significant role in NEC in newborn. Besides, target genes of miR-429/200a/b and miR-141/200c clusters were enriched in 11 signaling pathways. Vascular endothelial growth factor (VEGFA), E-selectin (SELE), kinase insert domain receptor (KDR), fms-related tyrosine kinase 1 (FLT1), and hepatocyte growth factor (HGF) were highly expressed in NEC in newborn, which were negatively regulated by miR-429/200a/b and miR-141/200c clusters and shared close association with disease genes. miR-429/200a/b and miR-141/200c clusters are poorly expressed while their target genes (VEGFA, SELE, KDR, FLT1, and HGF) are highly expressed in NEC in newborn, which might be identified as important biomarkers for this disease.

Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) Represses Proliferation of Trophoblast Cells in Rats with Preeclampsia via the MicroRNA-373/FLT1 Axis

“…Interestingly, NEAT1 knockdown can positively regulate FLT1 expression, and miR-373 inhibitor rescued the NEAT1 knockdown-induced reduction in FLT1 expression. FLT1 is 1 of the 2 receptors of vascular endothelial growth factor and is differentially expressed in necrotizing enterocolitis in newborns [ 25 ]. In addition, FLT1 expression is enhanced at the end of the first trimester [ 26 ].…”

Emerging Biomarkers for Prediction and Early Diagnosis of Necrotizing Enterocolitis in the Era of Metabolomics and Proteomics

“…Transcriptomics is the study of the transcriptome, e.g., the study of the mRNA within a cell or organism. Experimental and clinical studies as well as a metanalysis on long-non-coding RNA (lncRNA), micro RNA (miRNA), and mRNA profiles in NEC demonstrated a role of lncRNA, miRNA, and mRNA in NEC and suggested further evaluation of certain lncRNA and miRNA as potential biomarkers in NEC (45,(129)(130)(131)(132)(133).…”

Small RNA Sequencing Reveals Differentially Expressed miRNAs in Necrotizing Enterocolitis in Rats

“…NEC is also difficult to distinguish from other diseases with similar symptoms [ 6 , 7 ]. Recently, a systematic large-scale meta-analysis analyzed microRNA (miRNA) expression profiles to screen biomarkers for NEC in newborns [ 8 ]. Significant differential expression of miRNAs has been reported between ulcerative colitis and ulcerative colitis-related colorectal cancer in the mouse [ 9 ].…”

“…A recent study used a microarray to identify plasma miR-1290 as a novel biomarker that can effectively differentiate NEC from other diseases presenting similar symptoms, thus recognizing it as a potential therapeutic target [ 14 ]. miRNA-429/200a/b and miRNA-141/200c clusters, as well as miR-431, have also been identified as biomarkers of NEC through microarray analysis [ 8 , 15 ]. At present, the process of identification of aberrant miRNAs in animals with NEC using NGS technology is still at its nascent stage.…”