NOSIP promotes cell proliferation and motility by targeting SPTAN1 for ubiquitination and degradation in clear cell renal cell carcinoma.

Kidney cancer is one of the most common malignancies of the urinary system, with early surgical resection and molecular targeted therapy being the primary treatment options for clear cell renal cell carcinoma (ccRCC). Nitric oxide synthase interacting protein (NOSIP) has been implicated in several types of malignancies; however, its role in ccRCC remains elusive. In this study, we employed a variety of techniques, including transfection, co-immunoprecipitation (co-IP), real-time polymerase chain reaction (RT-PCR), Western blotting, ubiquitin assay, and animal experiments, to explore the role of NOSIP in renal cancer cells. Our results demonstrated that NOSIP interacts with SPTAN1 and promotes the progression of ccRCC by facilitating the ubiquitination and degradation of SPTAN1, thus downregulating its expression. Elevated SPTAN1 levels were found to inhibit the proliferation and metastasis of ccRCC, while the downregulation of SPTAN1 reversed the inhibition of cell survival caused by NOSIP knockdown. Moreover, xenograft studies in nude mice confirmed that NOSIP promotes tumor growth in vivo. This work identifies NOSIP as a key player in the proliferation and apoptosis of ccRCC and suggests that it contributes to malignancy of ccRCC by modulating SPTAN1 expression in an ubiquitination-dependent manner. Our findings provide a theoretical basis and experimental foundation for early diagnosis and molecular targeted therapy of ccRCC.