DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis
ObjectiveNecrotizing 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.MethodsDifferentially expressed (DE) miRN...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1480431/full |
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| author | Zhili Ding Ting Guo Qiang Tang Yaqiang Hong Zhibao Lv Li Lu Wenjun Zhuang |
| author_facet | Zhili Ding Ting Guo Qiang Tang Yaqiang Hong Zhibao Lv Li Lu Wenjun Zhuang |
| author_sort | Zhili Ding |
| collection | DOAJ |
| description | ObjectiveNecrotizing 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.MethodsDifferentially 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.ResultsPreliminarily, 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.ConclusionMiR-122-5p inhibition could impact arginine metabolism by targeting PRODH2 and ALDH18A1, thereby mitigating intestinal injury in NEC. |
| format | Article |
| id | doaj-art-0cd03f7239e540ef883f97bddf71fd5d |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-0cd03f7239e540ef883f97bddf71fd5d2025-01-22T07:11:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.14804311480431DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitisZhili Ding0Ting Guo1Qiang Tang2Yaqiang Hong3Zhibao Lv4Li Lu5Wenjun Zhuang6Department of General Surgery, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, Jiangsu, ChinaDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, Jiangsu, ChinaDepartment of General Surgery, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, Jiangsu, ChinaDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of General Surgery, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, Jiangsu, ChinaObjectiveNecrotizing 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.MethodsDifferentially 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.ResultsPreliminarily, 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.ConclusionMiR-122-5p inhibition could impact arginine metabolism by targeting PRODH2 and ALDH18A1, thereby mitigating intestinal injury in NEC.https://www.frontiersin.org/articles/10.3389/fgene.2024.1480431/fullneonatal necrotizing enterocolitismiR-122-5parginine metabolismintestinal stem cellbiomarker |
| spellingShingle | Zhili Ding Ting Guo Qiang Tang Yaqiang Hong Zhibao Lv Li Lu Wenjun Zhuang DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis Frontiers in Genetics neonatal necrotizing enterocolitis miR-122-5p arginine metabolism intestinal stem cell biomarker |
| title | DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| title_full | DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| title_fullStr | DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| title_full_unstemmed | DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| title_short | DEmiRNA-mRNA regulatory network reveals miR‐122-5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| title_sort | demirna mrna regulatory network reveals mir 122 5p as a regulatory factor of arginine metabolism in necrotizing enterocolitis |
| topic | neonatal necrotizing enterocolitis miR-122-5p arginine metabolism intestinal stem cell biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1480431/full |
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