BackgroundTheNuclear protein 1gene was first discovered in acute pancreatitis and functions as an oncogene in cancer progression and drug resistance. However, the role ofNuclear protein 1in bladder transitional cell carcinoma (BTCC) is still unclear.MethodsThe Cancer Genome Atlas database and immunohistochemical analysis were adopted to evaluateNuclear protein 1expression in BTCC. We applied lentivirus-mediated small-interfering RNA to down-regulate the expression ofNuclear protein 1in BTCC cell lines. We further performed an Affymetrix microarray and Gene Set Enrichment Analysis (GSEA) to assess the genes and signaling pathways related toNuclear protein 1.ResultsWe found thatNuclear protein 1expression was up-regulated in BTCC and positively related to the degree of BTCC malignancy. Compared with Caucasian patients with BTCC,Nuclear protein 1expression was attenuated in Asian patients. The Affymetrix microarray showed that lipopolysaccharide was the upstream regulatory factor ofNuclear protein 1in BTCC. The GSEA indicated thatNuclear protein 1expression was associated with signaling pathways in cancer, peroxisome proliferator-activated receptor (PPAR) pathways, and RNA degradation. The expression ofNuclear protein 1was negatively correlated with PPARG (R= −0.290,P< 0.001), but not with PPARA (R= 0.047,P= 0.344) and PPARD (R= −0.055,P= 0.260).ConclusionsThe study findings indicate thatNuclear protein 1is positively associated with the malignancy degree of BTCC and thatNuclear protein 1expression is negatively correlated with PPARG.