TRIM11 modulates sepsis progression by promoting HOXB9 ubiquitination and inducing the NF-κB signaling pathway.

Abstract

Introduction: The purpose of this investigation was to elucidate the functions of TRIM11 and HOXB9 in the pathogenesis of sepsis, focusing on their influence on inflammation, apoptosis, and the NF-κB signaling pathway.

Material and methods: Through public databases, TRIM family genes related to sepsis were screened, and TRIM11 was evaluated as a sepsis biomarker through ROC analysis. The UbiBrowser database screened TRIM11 downstream genes and identified HOXB9 as an essential target. THP-1 cells were stimulated by Lipopolysaccharide (LPS) to induce inflammation and simulate sepsis. Flow cytometry, Enzyme-linked immunosorbent assay, and Western blot experiments were used to detect changes in cell apoptosis rate, apoptosis-related proteins, and inflammatory cytokines after TRIM11 and HOXB9 were silenced. Additionally, we investigated the ubiquitination interaction between TRIM11 and HOXB9 and their effects on the NF-κB signaling pathway.

Results: Our findings demonstrated that sepsis patient samples had elevated levels of TRIM11 expression and had high clinical diagnostic value. Functional experiments showed that the knockdown of TRIM11 significantly alleviated LPS-induced THP-1 cell apoptosis and inflammation, while the knockdown of HOXB9 did the opposite. The simultaneous downregulation of TRIM11 and HOXB9 balanced these responses, suggesting they play a key role in regulating sepsis-associated inflammation and apoptosis. In addition, TRIM11 regulated the NF-κB signaling pathway by reversing HOXB9-induced activation through ubiquitination, suggesting a novel regulatory mechanism in the pathogenesis of sepsis.

Conclusions: Our findings highlight the interaction between TRIM11 and HOXB9 in regulating inflammation and apoptosis pathways, providing new insights into sepsis treatment.