TRIM38-mediated ubiquitination of IκBα promotes glioma development by activating the NF-κB signaling pathway

Introduction
Glioma constitutes approximately 50% of primary brain tumors. This study aimed to analyze the mechanism by which TRIM38 contributes to the progression of glioma.

Material and methods
The LN229 and T98G glioma cell lines were purchased. To evaluate cell malignant behaviors, Cell Counting Kit-8 (CCK-8) and Transwell assays were employed. Levels of TRIM38 and IkBa were quantified by RT-qPCR and Western blotting, respectively. Co-immunoprecipitation analyses were conducted to investigate the relationship between TRIM38 and IkBa.

Results
The findings demonstrated that TRIM38 was overexpressed in LN229 and T98G glioma cell lines. The silencing of TRIM38 inhibited malignant behaviors, whereas overexpression of TRIM38 had a stimulatory effect on these processes. Moreover, TRIM38 knockdown suppressed glioma growth in vivo. Co-immunoprecipitation assays confirmed that TRIM38 could bind to IkBa. Notably, TRIM38 increased the ubiquitination of IkBa, leading to its protein degradation and subsequent enhancement of IkBa phosphorylation, which activated the NF-kB pathway. JSH-23 treatment counteracted TRIM38 roles in glioma cells.

Conclusions
In summary, high levels of TRIM38 promoted glioma progression by increasing the ubiquitination of IkBa, thereby reducing IkBa protein stability and expression, and stimulating IkBa phosphorylation. This ultimately activated the NF-kB pathway, exacerbating the malignant behavior of glioma cells.