TRIM47 promotes cell viability, cell cycle progression, metabolic reprogramming, and inhibits apoptosis of glioma via the NF-κB signaling pathway

Background: Glioma is recognized as one of the most aggressive primary brain tumors with a poor prognosis. Although TRIM47 is linked to tumorigenesis in cancers, its role and the mechanisms involved in glioma are still not clear. The aim of this study is to elucidate the role and mechanism of TRIM47 in glioma.

Methods: TRIM47 expression in glioma tissues and glioma cell lines was assessed via immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. Cell Counting Kit-8 and flow cytometry assays evaluated cell viability, cell cycle, apoptosis, and glucose uptake. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured by Extracellular Flux Analyzer. Western blot detected alterations in cleaved caspase-3, pyruvate kinase M2, nuclear factor kappa B (NF-κB) and phosphorylation of NF-κB (p-NF-κB). Genetic knockdown/overexpression and NF-κB signaling pathway inhibitor treatment elucidated the regulatory mechanism of TRIM47 on tumor growth and metabolic reprogramming in male BALB/c nude mice and glioma cell lines.

Results: TRIM47 expression was found to be significantly increased in glioma tissues and cell lines. Moreover, elevated TRIM47 expression was linked to reduced overall survival in glioblastoma patients. The suppression of TRIM47 significantly reduced glioma cell viability, resulted in cell cycle arrest in the G1 phase, promoted apoptosis, increased OCR, and decreased ECAR, glucose uptake, and lactate production. Conversely, overexpression of TRIM47 enhanced glioma cell growth and metabolic reprogramming, which could be reversed by treatment with the NF-κB inhibitor PDTC. In vivo xenograft models showed that reducing TRIM47 expression significantly decreased tumor volume and weight and raised cell apoptosis.

Conclusions: Collectively, our findings indicate that TRIM47 promotes glioma progression through metabolic reprogramming and activation of the NF-κB signaling pathway, suggesting that TRIM47 is a potential therapeutic target for glioma treatment.