Correlation of serum miR-203a-3p with the severity of neonates with necrotizing enterocolitis and analysis of its molecular mechanism.

Abstract

Objectives: The objective of this study was to examine the role of microRNA-203a-3p (miR-203a-3p) in the pathogenesis of necrotizing enterocolitis (NEC).

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and receiver operating characteristic (ROC) curve analysis were employed to evaluate the relative abundances of miR-203a-3p as well as its diagnostic capacity. Logistic regression was applied to search for influential risk factors associated with NEC in neonates. Cell behaviors were assessed with flow cytometry and CCK-8 detection. The target genes of miR-203a-3p and its potential biological functions were analyzed via bioinformatic analysis.

Results: A significant reduction in serum levels of miR-203a-3p was observed in neonates with NEC. Notably, this miRNA exhibited exceptional diagnostic precision for differentiating NEC from non-NEC cases, as evidenced by an area under the curve (AUC) of 0.928. Furthermore, miR-203a-3p was established as an independent indicator for assessing the severity of NEC. In an NEC cell model, levels of miR-203a-3p were distinctly diminished; however, this decrease was significantly reversed following transfection with miR-203a-3p (p<0.001). Correspondingly, findings were noted regarding cell apoptosis, cell viability, inflammatory indicators, and antioxidant enzyme activities. MiR-203a-3p-related genes predominantly clustered within inflammatory-associated signaling pathways and proteins, particularly ataxia telangiectasia mutated (ATM). Notably, miR-203a-3p was found to directly target ATM. Importantly, heightened levels of ATM were detected in both neonates with NEC and LPS-triggered fetal human colon (FHC) cells (p<0.001).

Conclusions: MiR-203a-3p alleviates LPS-induced inflammatory damage in FHC cells through regulating ATM, thereby presenting a promising avenue for the development of novel therapeutic strategies for neonates with NEC.