RNF207 promotes the proliferation, migration and invasion of osteosarcoma through KCNQ1 mediated activation of ERK/MEK signaling pathway

Background

Ring finger protein 207 (RNF207) is an E3 ubiquitin ligase that regulates the stability and activity of target proteins via ubiquitination and non-proteolytic mechanisms. However, its role in osteosarcoma pathogenesis and association with patient prognosis remain poorly understood.

Methods

We integrated bioinformatics analyses of public databases with assayal validation in osteosarcoma cell lines and clinical tissue samples to assess RNF207 expression and its prognostic significance. Functional assays were performed to evaluate the impact of RNF207 knockdown or overexpression on osteosarcoma cell proliferation, migration, and invasion. Mechanistic insights were investigated through transcriptomic profiling, mass spectrometry, and co-immunoprecipitation assays. Finally, subcutaneous xenograft models were employed to validate RNF207's role in osteosarcoma progression in vivo.

Results

RNF207 was significantly upregulated in osteosarcoma cells and clinical specimens and correlated with adverse clinical outcomes. Genetic silencing of RNF207 suppressed osteosarcoma cell proliferation, migration, and invasion, whereas its overexpression enhanced these malignant phenotypes. Furthermore, RNF207 knockdown attenuated tumor growth in subcutaneous xenograft models. Mechanistically, RNF207 facilitated ubiquitin-mediated degradation of KCNQ1, thereby potentiating MAPK signaling pathway activation.

Conclusion

Clinically, elevated RNF207 expression in osteosarcoma patients serves as a biomarker for aggressive disease and unfavorable prognosis. Functionally, RNF207 drives osteosarcoma progression in vitro and in vivo by ubiquitinating and degrading KCNQ1 to hyperactivate MAPK signaling. These findings identify RNF207 as a novel therapeutic target and prognostic marker for osteosarcoma.