NUPR1 imparts oncogenic potential in bladder cancer

Abstract

Abstract Background NUPR1, or p8, is a small chromatin protein that plays a central role in the resistance to treatment and progression of cancer. Nevertheless, the molecular mechanism of NUPR1 in bladder cancer (BLCA) remains unclear. Methods We used online databases and immunohistochemistry (IHC) to explore the expression of NUPR1 in BLCA tissues and controls. Lentivirus‐mediated small interfering ribonucleic acid (siRNA) was used to knockdown the expression of NUPR1 in two human BLCA cell lines. We used an in vivo experiment to investigate the effect of NUPR1 knockdown on the growth of BLCA. Moreover, an in silico analysis was conducted to assess the differential expression profile after NUPR1 interference. The CIBERSORT algorithm was utilized to evaluate the effects of tumor‐infiltrating immune cells among BLCA patients. Results The expression of NUPR1 in BLCA tissues was significantly higher than in the control. NUPR1 expression was also positively correlated with the stage of BLCA. After lentivirus‐mediated interference, the expression of NUPR1 was significantly down‐regulated in BLCA cell lines. The cell cycle was blocked in G1 phase and the cell proportion of S phase was decreased in both two cell lines. Moreover, in vivo experiment revealed that the tumor growth of BLCA can be delayed by inhibiting the expression of NUPR1. Both in silico analysis and functional experiments revealed that NUPR1 was correlated with epithelial–mesenchymal transition (EMT). We also revealed that macrophages were the most related immune cells associated with the expression of NUPR1 in BLCA. Conclusions This study suggests that NUPR1 plays a carcinogenic role in BLCA. NUPR1 lentivirus‐mediated interference could interfere with cycle progression of the BLCA cell, resulting in cell cycle arrest in the G1‐phase. The carcinogenic effect of NUPR1 in BLCA is likely achieved through EMT. NUPR1 is correlated with the M0‐type macrophage markers CD68 and CD11b‐integrin.

Keywords

• bladder cancer
• expression
• invasion
• NUPR1