PUS1 facilitates cell migration in clear cell renal cell carcinoma through the promotion of mRNA pseudouridylation and the stabilization of the SMOX gene

Clear cell renal cell carcinoma (ccRCC) is a highly aggressive malignancy characterized by its propensity for metastasis. Pseudouridine synthase 1 (PUS1), an enzyme involved in RNA modification, has been implicated in cancer progression, but its role in ccRCC remains unclear. This study investigates PUS1's role in ccRCC and evaluates its potential as a prognostic biomarker and therapeutic target. We assessed PUS1 expression in 541 ccRCC samples from The Cancer Genome Atlas (TCGA) and utilized Receiver Operating Characteristic (ROC) analyses to determine its prognostic value. High PUS1 levels were associated with reduced overall and disease-specific survival in ccRCC patients. Functional assays demonstrated that PUS1 promotes cell migration by stabilizing SMOX mRNA via pseudouridylation. The transcription factor USF1 regulates PUS1 expression by binding to its promoter region, enhancing its transcriptional activity. PUS1 silencing in ccRCC cell lines significantly reduced cell migration, while its overexpression had the opposite effect. These findings implicate the USF1-PUS1-SMOX signaling axis in regulating the migratory abilities of ccRCC cells. In conclusion, PUS1 plays a pivotal role in ccRCC progression and serves as an independent prognostic biomarker. Targeting PUS1 may offer promising therapeutic strategies for ccRCC patients. Further research is needed to explore its function in other cancers and to clarify its underlying molecular mechanisms.