Mechanism study of RBX1 promoting renal clear cell carcinoma invasion, immune suppression, and sunitinib resistance

Clear cell renal cell carcinoma (ccRCC) often exhibits drug resistance, highlight_x0002_ing the need to identify novel therapeutic targets. RING box protein 1 (RBX1), an E3 ubiquitin ligase associated with tumor progression, has an unclear role in ccRCC. This study investigated the clinical significance, molecular mech_x0002_anisms, and role of RBX1 in treatment resistance through multi-omics and functional analyses. Analysis of The Cancer Genome Atlas (TCGA) data revealed that RBX1 is overexpressed in ccRCC and is associated with advanced dis_x0002_ease stages and poor prognosis. Functional enrichment studies linked RBX1 to processes such as cytoskeletal remodeling,extracellular matrix deposition, and lipid metabolism disorders.Additionally, tumors with high RBX1 expression exhibit an immunosuppressive microenvironment characterized by increased reg_x0002_ulatory T cells (Tregs) and elevated expression of immune checkpoint markers (LAG3/Galectin-9). In vitro experiments confirmed that RBX1 promotes ccRCC proliferation, migration, and invasion while conferring resistance to the standard targeted therapy drug sunitinib. Our findings suggest that RBX1 may serve as a key driver of ccRCC invasiveness and immune suppression. These discoveries indicate that RBX1 has the potential to become a prognostic biomarker and a target for precision therapy in advanced ccRCC.