NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-&amp;#x003ba;B/P53 functional balance

Jian WANG; Congcong DING; Yan LU; Tong LI

doi:10.19401/j.cnki.1007-3639.2022.07.005

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NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-κB/P53 functional balance

Article | 更新时间：2025-12-31

- NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-κB/P53 functional balance
- China Oncology Vol. 32, Issue 7, Pages: 614-623(2022)
- 作者机构：
  
  广东医科大学广东省医学分子诊断重点实验室,广东东莞 523808
- 作者简介：
  
  WANG Jian, E-mail: wangjian20031228@126.com.
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.07.005
  CLC： R737.25
- Received：29 November 2021，
  
  Published：30 July 2022
- 稿件说明：
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Jian WANG, Congcong DING, Yan LU, et al. NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-κB/P53 functional balance[J]. China Oncology, 2022, 32(7): 614-623.
DOI：

Jian WANG, Congcong DING, Yan LU, et al. NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-κB/P53 functional balance[J]. China Oncology, 2022, 32(7): 614-623. DOI： 10.19401/j.cnki.1007-3639.2022.07.005.

摘要

背景与目的：

前列腺炎症是促进其癌变的一个重要因素

但关键的分子机制不明。Nemo样激酶（Nemo-like kinase

NLK）在前列腺癌组织中的表达水平较良性组织显著降低

并且在前列腺癌细胞中沉默NLK表达可增强核因子-

#x003ba;B（nuclear factor-

#x003ba;B

NF-

#x003ba;B）的转录活性。本研究旨在探讨NLK调控前列腺炎-癌转化的作用及其机制

为应用抗炎新策略预防前列腺癌提供新的分子靶点和理论依据。

方法：

采用人前列腺上皮细胞RWPE-1与人急性单核细胞白血病细胞THP-1共培养的方法建立前列腺炎-癌转化细胞模型（RWPE-1/THP-1）。采用MTT实验及软琼脂集落形成实验检测

NLK

基因沉默或过表达对模型细胞增殖及恶性转化能力的影响。采用双荧光素酶报告基因实验检测

NLK

基因沉默或过表达对模型细胞NF-

#x003ba;B转录活性的影响。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction

RTFQ-PCR）和蛋白质印迹法（Western blot）检测

NLK

基因沉默或过表达对模型细胞中核受体相关因子1（nuclear receptor-related fa

ctor 1

Nurr1）和鼠双微体基因2（murine double minute 2

MDM2）的mRNA表达和蛋白水平的影响。采用Western blot检测

NLK

基因沉默或过表达对模型细胞P53蛋白表达水平的影响。采用免疫荧光和免疫共沉淀技术分别检测Nurr1蛋白和P53蛋白在RWPE-1细胞中的定位分布及相互作用情况。

结果：

与RWPE-1/THP-1组相比

RWPE-1（NLK

#x02191;）/THP-1组的细胞增殖及转化能力显著降低

NF-

#x003ba;B转录活性显著减弱

Nurr1和MDM2的mRNA表达和蛋白水平显著下调

P53蛋白表达水平显著上升（

0.05）;与之相反

RWPE-1（NLK

#x02193;）/THP-1组的细胞增殖及转化能力显著升高

NF-

#x003ba;B转录活性显著增强

Nurr1和MDM2的mRNA表达和蛋白水平显著上调

P53蛋白表达水平显著下降（

0.05）。此外

Nurr1蛋白与P53蛋白在RWPE-1细胞的细胞核中存在共定位及相互作用。

结论：

NLK抑制前列腺炎-癌转化可能依赖于其对NF-

#x003ba;B/P53平衡的维护。

Abstract

Background and purpose:

Prostate inflammation is an important promoter of carcinogenesis. However

the key underlying mechanisms remain unknown. Nemo-like kinase (NLK) expression is significantly lower in prostate cancer tissues than in benign tissues; downregulation of NLK expression can enhance the transcriptional activity of nuclear factor-

#x003ba;B (NF-

#x003ba;B) in prostate cancer cells. This study aimed to explore the effects of NLK in regulating the transformation from prostatitis to prostate cancer and its mechanisms

to provide effective molecular targets and a new theoretical basis for novel anti-inflammatory strategies in prostate cancer prevention.

Methods:

The cell model of transformation from prostatitis to prostate cancer (RWPE-1/THP-1) was established by co-culture of human prostate epithelial cells RWPE-1 and human acute monocytic leukemia cells THP-1. The proliferation and transformation abilities of model cells with the silence or overexpression of NLK were investigated by MTT experiment and soft agar experiment

respectively. The effects of the silence or overexpression of NLK on NF-

#x003ba;B activity in model cells were investigated by luciferase assay. The mRNA expression and protein levels of nuclear receptor-related factor 1 (Nurr1) and murine double minute 2 (M

DM2) in model cells with the silence or overexpression of NLK were validated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot

respectively. The effects of the silence or overexpression of NLK on P53 protein levels in model cells were investigated by Western blot. The co-localization of Nurr1 and P53 in RWPE-1 cells was investigated by immunofluorescence experiment. The interaction between Nurr1 and P53 in RWPE-1 cells was verified by co-immunoprecipitation assay.

Results:

Compared with the RWPE-1/THP-1 group

the proliferation and transformation abilities of model cells were decreased

the NF-

#x003ba;B activity was inhibited

the mRNA expression and protein levels of the Nurr1 and MDM2 were down-regulated

and the P53 protein levels were increased in RWPE-1 (NLK

#x02191;)/THP-1 group (

0.05). In contrast

the proliferation and transformation abilities of model cells were increased

the NF-

#x003ba;B activity was enhanced

the mRNA expression and protein levels of the Nurr1 and MDM2 were up-regulated

and the P53 protein levels were reduced in RWPE-1 (NLK

#x02193;)/THP-1 group (

0.05). Moreover

the Nurr1 and P53 were co-located in the nucleus of RWPE-1 cells and they interacted with each other.

Conclusion:

NLK can inhibit the transformation from prostatitis to prostate cancer

which may be related to maintaining NF-

#x003ba;B/P53 functional balance.

关键词

Keywords

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NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-&#x003ba;B/P53 functional balance

DOI：10.19401/j.cnki.1007-3639.2022.07.005

摘要

Abstract

关键词

Keywords

references

NLK inhibits the transformation from prostatitis to prostate cancer through maintaining NF-κB/P53 functional balance