NUPR1 imparts oncogenic potential in bladder cancer

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)...

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Main Authors: Lifeng Zhang, Shenglin Gao, Xiaokai Shi, Yin Chen, Shuzhang Wei, Yuanyuan Mi, Li Zuo, Chunjian Qi
Format: Article
Language:English
Published: Wiley 2023-03-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5518
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author Lifeng Zhang
Shenglin Gao
Xiaokai Shi
Yin Chen
Shuzhang Wei
Yuanyuan Mi
Li Zuo
Chunjian Qi
author_facet Lifeng Zhang
Shenglin Gao
Xiaokai Shi
Yin Chen
Shuzhang Wei
Yuanyuan Mi
Li Zuo
Chunjian Qi
author_sort Lifeng Zhang
collection DOAJ
description 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.
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spelling doaj.art-3fa7215846ae480e9f0b2dcffb6dc3dc2023-04-02T20:55:00ZengWileyCancer Medicine2045-76342023-03-011267149716310.1002/cam4.5518NUPR1 imparts oncogenic potential in bladder cancerLifeng Zhang0Shenglin Gao1Xiaokai Shi2Yin Chen3Shuzhang Wei4Yuanyuan Mi5Li Zuo6Chunjian Qi7Department of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaDepartment of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaDepartment of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaDepartment of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaDepartment of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaDepartment of Urology Affiliated Hospital of Jiangnan University Wuxi ChinaDepartment of Urology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaMedical Research Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical University Changzhou ChinaAbstract 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.https://doi.org/10.1002/cam4.5518bladder cancerexpressioninvasionNUPR1
spellingShingle Lifeng Zhang
Shenglin Gao
Xiaokai Shi
Yin Chen
Shuzhang Wei
Yuanyuan Mi
Li Zuo
Chunjian Qi
NUPR1 imparts oncogenic potential in bladder cancer
Cancer Medicine
bladder cancer
expression
invasion
NUPR1
title NUPR1 imparts oncogenic potential in bladder cancer
title_full NUPR1 imparts oncogenic potential in bladder cancer
title_fullStr NUPR1 imparts oncogenic potential in bladder cancer
title_full_unstemmed NUPR1 imparts oncogenic potential in bladder cancer
title_short NUPR1 imparts oncogenic potential in bladder cancer
title_sort nupr1 imparts oncogenic potential in bladder cancer
topic bladder cancer
expression
invasion
NUPR1
url https://doi.org/10.1002/cam4.5518
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