RNF214 silencing attenuates prostate cancer progression and modulates mTOR signaling through CAV1 ubiquitination.

Although both RNF214 and CAV1 are implicated in tumor progression and signaling regulation, the role of the RNF214-CAV1 axis in prostate cancer (PCa) remains unclear. This study aims to explore how RNF214 modulates CAV1 stability via ubiquitination and its influence on PCa progression and mTOR signaling. The expression patterns and functional impact of RNF214 were assessed using clinical PCa tissues, cultured cell lines, and mouse xenograft models. Gene silencing experiments were conducted to evaluate effects on cell proliferation, migration, and signaling activity. Protein interactions and ubiquitination were examined via GST pull-down and co-immunoprecipitation. Immunohistochemistry was used to assess proliferation and pathway markers in vivo. RNF214 expression was elevated in PCa samples, whereas CAV1 was downregulated, with an inverse correlation observed at both transcript and protein levels. RNF214 knockdown inhibited proliferation and migration of PCa cells, accompanied by upregulation of CAV1. A direct interaction between RNF214 and CAV1 was confirmed, and CAV1 ubiquitination was enhanced by RNF214. Dual knockdown of RNF214 and CAV1 restored cell growth and mTOR pathway activity, including phosphorylation of 4EBP1, S6K1, and S6. In xenograft models, tumor suppression induced by RNF214 silencing was reversed by CAV1 co-depletion. Immunohistochemistry showed corresponding changes in Ki67, PTEN, and CAV1 expression. RNF214 promotes prostate tumor progression by ubiquitinating and targeting CAV1 for degradation, thereby sustaining mTOR signaling. These findings highlight the RNF214-CAV1 axis as a potential therapeutic target in PCa.