IRF2BPL inhibits proliferation, migration and invasion of osteosarcoma cells by inhibiting FOSL2-mediated PI3K/AKT...

Interferon regulatory factor 2-binding protein-like protein (IRF2BPL) is a nuclear protein susceptible to degradation and phosphorylation. It modulates downstream protein expression and facilitates ubiquitin-mediated proteolysis. Although IRF2BPL has been investigated in various biological systems, its functional role in osteosarcoma pathogenesis remains poorly understood.

We analyzed publicly available databases to evaluate IRF2BPL expression in osteosarcoma tissues and its prognostic significance. In vitro functional assays, including CCK-8, wound healing, and Transwell experiments, were conducted to examine IRF2BPL's effects on osteosarcoma cell proliferation, migration, and invasion. RNA sequencing (RNA-seq) and co-immunoprecipitation (Co-IP) assays were used to investigate IRF2BPL's molecular mechanisms. A subcutaneous xenograft tumor model was generated to validate its role in vivo.

IRF2BPL is downregulated in osteosarcoma and correlates with patient survival. Overexpression of IRF2BPL suppresses osteosarcoma cell proliferation, migration, and invasion, whereas its silencing enhances these processes, both in vitro and in vivo. Mechanistic studies revealed that IRF2BPL influences osteosarcoma progression by regulating the FOSL2/PI3K/AKT/mTOR axis via ubiquitin-mediated degradation.

In summary, our study demonstrates that IRF2BPL is downregulated in osteosarcoma and serves as a prognostic marker. Functional assays confirmed that IRF2BPL suppresses tumor cell proliferation, migration, and invasion, while its silencing exerts the opposite effect. Mechanistically, IRF2BPL regulates the FOSL2/PI3K/AKT/mTOR axis through ubiquitin-mediated degradation, highlighting its potential as a therapeutic target in osteosarcoma.