Multi-Omics Dissection of the Role of Ubiquitination Modification in Post-Stroke Neuroinflammation and Function Damage.

Abstract

Objective: This study aims to explore the role of ubiquitination in neuroinflammation and functional damage after stroke using multi-omics analysis, focusing on the pathways influenced by ubiquitination.

Methods: Gene expression data related to stroke were collected from the GEO database. Differentially expressed genes were identified using the "limma" package in R. GO and KEGG enrichment analyses were performed to identify significant pathways. Ubiquitination data were integrated with differential gene data to identify genes with ubiquitination sites, focusing on those that bind to E3 ligases. Network analysis was conducted to examine the interactions among ubiquitin-modified proteins, and protein-RNA correlations were analyzed using data from proteomic analysis.

Results: The analysis identified several inflammatory pathways significantly altered after stroke, including the NF-κB, TNF, and NOD-like receptor signaling pathways. A total of 113 genes with ubiquitination sites were found to be associated with E3 ligases and stroke-related genes. Among them, TRIM37 and TRIM25 emerged as key regulatory factors. Protein interaction network analysis revealed that ubiquitination modifications enhance neuroinflammation, leading to functional impairments. Post-translational modifications, indicated by higher protein stability, were observed in the proteins with the most ubiquitination sites, supporting their potential as therapeutic targets.

Discussion: The study identifies TRIM37 and TRIM25 as crucial regulators of neuroinflammation through ubiquitination after stroke. These findings suggest that ubiquitination plays a significant role in stroke pathology and could serve as therapeutic targets for stroke treatment.