promotes the progression of clear cell renal cell carcinoma via the TNF-α/NF-κB axis.

Background: Clear cell renal cell carcinoma (ccRCC) represents the predominant form of kidney cancer. The Ras homology (Rho) GTPases family plays essential roles in several tumors. However, few studies have reported the function and clinical value of the Rho GTPases family in ccRCC. Our study aimed to systematically investigate the expression profiles, functional roles, and clinical significance of Rho GTPases in ccRCC, with the goal of identifying potential biomarkers and novel therapeutic targets to improve the treatment outcomes and survival rates of this aggressive kidney cancer.

Methods: The expression level of Ras homolog family member J () was detected in ccRCC cells and tissues using quantitative polymerase chain reaction (qPCR), western blotting, and immunohistochemistry (IHC). The biological functions of were evaluated via and assays. RNA sequencing was used to investigate the underlying mechanisms. Potential inhibitors were identified using virtual screening in a Food and Drug Administration (FDA)-approved drugs repository.

Results: Our study identified as the only Ras-homologous guanosine triphosphate (GTP)-binding protein (Rho GTPase) associated with poor prognosis in ccRCC patients. Using ccRCC cells and tumor tissues, we found that was significantly highly expressed in ccRCC. Moreover, apparently enhanced ccRCC cell proliferation, migration, and invasion. Further, upregulated could accelerate cell cycle progression, inhibit apoptosis, and enhance epithelial-mesenchymal transition (EMT). Through orthotopic tumor models, we found that knocking down inhibited tumor growth. Mechanically, influenced ccRCC progression through the tumor necrosis factor-alpha/nuclear factor kappa B (TNF-α/NF-κB) axis. Blocking this axis could partially rescue malignant phenotypes caused by . Finally, since there are no available drugs targeting , the virtual screening was used to identify potential inhibitors based on an FDA-approved drug library, which showed that ergotamine, irinotecan, ledipasvir, pazopanib, and avodart were potential -targeting drugs.

Conclusions: Taken together, our findings provide novel insights into the role of and identify available potential drugs for controlling ccRCC.