These findings not only illustrate the regulatory mechanism of miR-129-5p and SPN in the progression of ccRCC, providing novel potential therapeutic targets for ccRCC, but also greatly deepen our knowledge about the effect of SPN on the progression of cancers and its upstream regulatory mechanism, bringing additional insight into the exploration of new biomarkers and target therapies for ccRCC. Here, SPN is linked to nonpapillary renal cell carcinoma.