Specific miRNA and its target in neutrophils after traumatic injury
Jun Yang1, Huazhong Han1, Yijun Zhao1
1Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Abstract:
Traumatic injury is a leading cause of mortality and morbidity. MicroRNAs (miRNAs) regulate the cellular responses when traumatic injury occurs. Previously, we reported that miR-3945, miR-125a-5p, miR-363-3p, and miR-150-5p were significantly altered in neutrophils of patients who suffered traumatic injury. In the present study, by comparing neutrophils of patients suffering from major trauma with neutrophils of patients with a inflammatory disease, we found that the variation trend of miR-150-5p was relatively different in the process of these two diseases. Gene Ontology and pathway analysis of miR-150-5p revealed that it may activate the mitogen-activated protein kinase and Toll-like receptor signaling pathways and cell adhesion molecules when the traumatic injury occurs. In addition, protein kinase C alpha (PRKCA) was also identified as a direct target of miR-150-5p by establishing a miRNA-mRNA network, and this target was validated via dual-luciferase reporter and western blot analysis. Our results suggested that the expression of miR-150-5p was down-regulated in neutrophils after a major traumatic injury. miR-150-5p and its identified target PRKCA play important roles in the development of traumatic process.
Insights
MicroRNA-150-5p (miR-150-5p) is down-regulated in neutrophils following major traumatic injury. This microRNA and its target, protein kinase C alpha (PRKCA), are crucial in the traumatic injury process.
Area of Science:
- Molecular Biology
- Immunology
- Trauma Research
Background:
- Traumatic injury significantly contributes to mortality and morbidity.
- MicroRNAs (miRNAs) are key regulators of cellular responses to trauma.
- Previous work identified altered miRNA profiles in neutrophils post-trauma.
Purpose of the Study:
- To investigate the role of miR-150-5p in neutrophils following major traumatic injury.
- To compare the expression patterns of miR-150-5p in trauma versus inflammatory disease.
- To identify downstream targets and pathways regulated by miR-150-5p in trauma.
Main Methods:
- Comparative analysis of neutrophil miRNA expression in trauma patients versus inflammatory disease patients.
- Bioinformatic analysis (Gene Ontology, pathway analysis) for miR-150-5p.
- Construction and validation of a miRNA-mRNA network for miR-150-5p.
- Dual-luciferase reporter and Western blot assays to validate protein kinase C alpha (PRKCA) as a direct target.
Main Results:
- miR-150-5p showed distinct variation trends in trauma compared to inflammatory disease.
- miR-150-5p potentially activates MAPK, Toll-like receptor signaling, and cell adhesion molecules.
- Protein kinase C alpha (PRKCA) was identified and validated as a direct target of miR-150-5p.
- Expression of miR-150-5p was found to be down-regulated in neutrophils after major traumatic injury.
Conclusions:
- Down-regulation of miR-150-5p in neutrophils is a feature of major traumatic injury.
- miR-150-5p and its target PRKCA play significant roles in the pathophysiology of traumatic injury.
- These findings offer potential targets for therapeutic interventions in trauma management.
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