Abstract
Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.
Highlights
Necrotizing enterocolitis (NEC) is considered one of the leading causes of neonatal morbidity and mortality [1]
Pathological changes in intestinal architecture were assessed according to the NEC scoring system [17]
H&E staining of the ileocecum revealed that the control group had no abnormal histological changes; the epithelium was intact and continuous; the glands were arranged neatly; the villi were very high; and there was no hyperemia and edema in the mucosa, submucosa, and lamina propria
Summary
Necrotizing enterocolitis (NEC) is considered one of the leading causes of neonatal morbidity and mortality [1]. NEC is common in neonates and premature infants, especially in very low birth weight infants, with a death rate of approximately 30% [2, 3]. It is difficult to diagnose early clinical NEC, given its nonspecific clinical features such as acute phase proteins and cytokines. NEC is difficult to distinguish from other diseases with similar symptoms [6, 7]. A systematic large-scale meta-analysis analyzed microRNA (miRNA) expression profiles to screen biomarkers for NEC in newborns [8]. Little is known about the role (and related molecular mechanism) of miRNAs in NEC. It is of great importance to screen novel miRNA biomarkers to diagnose NEC
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