RNF130 inhibits the proliferation, migration and invasion of osteosarcoma through DAB1 mediated suppression of the PI3K/AKT signaling pathway

Background: Ring finger protein 130 (RNF130) is also known as Goliath. It is the mammalian homolog of the Drosophila E3 Ligase Goliath (dGoliath), which is localized to the protease-associated (PA) domain. Although RNF130 has been investigated in Other research areas, its functional role in osteosarcoma remains poorly defined.

Methods: We initially analyzed the expression of RNF130 in osteosarcoma via an online database and explored its association with patient survival prognosis. Subsequently, the influence of RNF130 on osteosarcoma malignancy was verified using in vivo phenotypic assays. Furthermore, the molecular mechanism underlying RNF130-mediated regulation of osteosarcoma progression was elucidated by transcriptome Sequencing and co-immunoprecipitation. Finally, a xenograft tumor model was constructed in nude mice to verify the regulatory effect of RNF130 on osteosarcoma growth in vivo.

Results: RNF130 expression was significantly decreased in osteosarcoma tissues and was associated with overall survival in the TCGA dataset. Functional assays demonstrated that overexpression of RNF130 inhibits the proliferation, migration, and invasion of osteosarcoma cells. Conversely, silencing of RNF130 promoted these malignant phenotypes. Mechanistic investigations revealed that RNF130 functions as a tumor suppressor in osteosarcoma by regulating the DAB1/PI3K/Akt/mTOR signaling axis via the ubiquitin-proteasome pathway.

Conclusion: RNF130 may be associated with prognosis in osteosarcoma and suppresses malignant progression by regulating the DAB1/PI3K/Akt/mTOR signaling pathway. Its clinical prognostic value still requires validation in larger independent datasets.

DAB1; Osteosarcoma; PI3K/AKT/mTOR signaling pathway; RNF130; Ubiquitin-proteasome degradation pathway.