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ORIGINAL RESEARCH article

Front. Genet.
Sec. RNA
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1480431

DEmiRNA-mRNA regulatory network reveals miR-122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis

Provisionally accepted
Zhili Ding Zhili Ding 1Ting Guo Ting Guo 2*Qiang Tang Qiang Tang 1*Yaqiang Hong Yaqiang Hong 1*Zhi Bao Lv Zhi Bao Lv 2Li Lu Li Lu 2*Wenjun Zhuang Wenjun Zhuang 1*
  • 1 Changzhou Children's Hospital, Changzhou, China
  • 2 Shanghai Children's Hospital, Shanghai, Shanghai Municipality, China

The final, formatted version of the article will be published soon.

    Objective: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency with relatively high morbidity and mortality in neonates. The role of microRNAs (miRNAs) in NEC is not yet entirely clear. This study aimed to explore the mechanism of miR-122-5p in NEC.Methods: Differentially expressed (DE) miRNAs were sequenced in control and NEC mice. The DEmiRNA-mRNA regulatory network was constructed and the bioinformatics analysis was performed to identify the target mRNAs and potential roles of the DEmiRNAs. The miR-122-5p activation was explored in vitro in the human intestinal epithelial cell (FHs74Int) and rat intestinal epithelial cell (IEC-6). In vivo, mice were transinfected with miR-122-5p inhibitor before the NEC occurred. Mass spectrometry was used to qualify the concentrations of amino acids, and the viability of intestinal stem cell (ISC) was accessed to verify the biological function.Results: Preliminarily, 15 miRNAs were found to be differentially expressed between NEC group and control group. Subsequent bioinformatics analysis revealed that miR-122-5p significantly contributes to the arginine metabolism in NEC through the DEmiRNA-mRNA regulatory network, with PRODH2 and ALDH18A1 being identified as its target genes. In vitro, miR-122-5p mimic inhibited the expression of PRODH2 and ALDH18A1 in the FHs74Int cells and IEC-6 cells. In vivo, inhibition of miR-122-5p led to increased expression of PRODH2 and ALDH18A1, along with elevated arginine levels. Following transfection with a miR-122-5p inhibiting adenovirus, the survival rate of NEC mice improved, and intestinal injury was alleviated.MiR-122-5p inhibition could impact arginine metabolism by targeting PRODH2 and ALDH18A1, thereby mitigating intestinal injury in NEC.

    Keywords: Neonatal necrotizing enterocolitis, miR-122-5p, arginine metabolism, intestinal stem cell, biomarker

    Received: 16 Aug 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Ding, Guo, Tang, Hong, Lv, Lu and Zhuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ting Guo, Shanghai Children's Hospital, Shanghai, 200062, Shanghai Municipality, China
    Qiang Tang, Changzhou Children's Hospital, Changzhou, China
    Yaqiang Hong, Changzhou Children's Hospital, Changzhou, China
    Li Lu, Shanghai Children's Hospital, Shanghai, 200062, Shanghai Municipality, China
    Wenjun Zhuang, Changzhou Children's Hospital, Changzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.