miR-124在膀胱癌中的表达及其临床意义

王阳; 胡跃世; 李征; 朱清; 段启新; 刘磊; 马慧利; 李明林

doi:10.16016/j.1000-5404.201912083

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miR-124在膀胱癌中的表达及其临床意义

临床医学 | 更新时间：2026-01-09

- miR-124在膀胱癌中的表达及其临床意义
- Expression of microRNA-124 in bladder cancer and its clinical significance
- 第三军医大学学报 2020年42卷第10期页码：1035-1041
- 作者机构：
  
  1.473009 河南南阳，河南省南阳市中心医院：泌尿外科
  2.473009 河南南阳，河南省南阳市中心医院：肿瘤内科
- 作者简介：
  
  [李明林，E-mail：liminglinvip@126.comLI Minglin, E-mail:liminglinvip@126.com
- 基金信息：
- DOI：10.16016/j.1000-5404.201912083
  中图分类号： R394.3;R730.23;R737.14
- 收稿：2019-12-10，
  
  修回：2020-03-13，
  
  纸质出版：2020-05-30
- 稿件说明：
移动端阅览
王阳, 胡跃世, 李征, 等. miR-124在膀胱癌中的表达及其临床意义[J]. 第三军医大学学报, 2020,42(10):1035-1041.

Yang WANG, Yueshi HU, Zheng LI, et al. Expression of microRNA-124 in bladder cancer and its clinical significance[J]. Journal of Third Military Medical University, 2020, 42(10): 1035-1041.
王阳, 胡跃世, 李征, 等. miR-124在膀胱癌中的表达及其临床意义[J]. 第三军医大学学报, 2020,42(10):1035-1041. DOI： 10.16016/j.1000-5404.201912083.

Yang WANG, Yueshi HU, Zheng LI, et al. Expression of microRNA-124 in bladder cancer and its clinical significance[J]. Journal of Third Military Medical University, 2020, 42(10): 1035-1041. DOI： 10.16016/j.1000-5404.201912083.

摘要

目的

探讨miR-124在膀胱癌中的表达及其临床意义。

方法

RT-qPCR检测人正常膀胱尿路上皮细胞SV-HUC-1及膀胱癌细胞(5637、J82、T24、TCCSUP、UM-UC-3)中miR-124的表达；收集本院2013年1月至2016年1月114例膀胱癌患者的术后组织标本，采用原位杂交法检测miR-124在膀胱癌及癌旁组织中的表达，并分析其与临床病理特征及预后的相关性。细胞试验分3组：分别将miRNA-NC(miRNA-NC组)、miRNA-124 mimics(miRNA-124 mimics组)和miR-124 inhibitor(miR-124 inhibitor组)转染至膀胱癌T24细胞，CCK-8试验检测miR-124表达对细胞增殖能力的影响，Western blot检测其增殖相关蛋白(PCNA、Ki-67)和p-AKT表达。

结果

qPCR结果显示，miR-124在膀胱癌细胞5637、J82、T24、TCCSUP、UM-UC-3中的表达均低于正常膀胱尿路上皮细胞SV-HUC-1(

0.05)；原位杂交试验结果显示，miR-124在正常膀胱尿路上皮细胞中呈高表达，在非浸润性和浸润性膀胱癌组织中低表达；miR-124表达与膀胱癌临床T分期、淋巴结转移及肿瘤分化程度密切相关(

=6.829，

=0.009；

=6.844，

=0.009；

=5.111，

=0.024)；Kaplan-Meier分析显示，miR-124低表达组患者的总生存率(OS)和无病生存期(DFS)明显低于高表达组患者(

=22.7

0.01；

=26.57

0.01)。多因素分析结果表明miR-124低表达是影响膀胱癌患者预后的独立危险因素(OS HR=4.63; 95%

:1.39~7.23;

=0.007; DFS HR=5.82; 95%

: 1.56~11.42;

=0.003)。与miRNA-NC组比较，miR-124mimics组T24细胞增殖能力明显下降(

0.05)，增殖相关蛋白(PCNA、Ki-67)和p-AKT表达量明显降低(

0.05)；而miR-124 inhibitor组中T24细胞增殖能力增强，PCNA、Ki-67及p-AKT的蛋白表达量升高(

0.05)。

结论

miR-124在膀胱癌细胞及组织中低表达，并促进膀胱癌细胞的增殖能力，低表达miR-124的膀胱癌患者预后较差，其机制可能与AKT信号通路的激活有关。

Abstract

Objective

To investigate the expression of microRNA-124 (miR-124) in bladder cancer and its clinical significance.

Methods

The expression of miR-124 in a normal bladder urothelial cell line (SV-HUC-1) and 5 bladder cancer cell lines (5 637

J82

T24

TCCSUP and UM-UC-3) was detected using RT-qPCR. We also detected the expression of miR-124 using

in situ

hybridization in 114 tissue specimens of bladder cancer and adenocarcinoma tissues from patients undergoing surgeries in our hospital between January

2013 and January

2016. The correlations of miR-124 expression with the clinicopathological characteristics and prognosis of the patients were analyzed. In the

in vitro

experiment

we tested the effect of transfection with miR-124 mimics and miR-124 inhibitor on the proliferation of bladder cancer T24 cells using CCK-8 assay and on the cellular expression of PCNA

Ki-67 and p-AKT using Western blotting.

Results

The expression of miR-124 in the 5 bladder cancer cell lines was significantly lower than that in normal bladder urothelial cells. The results of

in situ

hybridization showed that miR-124 was highly expressed in normal bladder urothelial cells but lowly expressed in non-invasive and invasive bladder cancer tissues. The expression of miR-124 was closely correlated with clinical T stage (

Chi

-square=6.829

=0.009)

lymph node metastasis (

Chi

-square= 6.844

=0.009) and tumor differentiation (

Chi

-square=5.111

=0.024). Kaplan-Meier analysis showed that compared with those with a high expression of miR-124

the patients with a low expression of miR-124 had significantly shorter overall survival (

Chi

-square=22.7

0.01) and disease-free survival (

Chi

-square=26.57

0.01). Multivariate analysis showed that a low expression of miR-124 was an independent risk factor for a poor prognosis in patients with bladder cancer in terms of both th

e overall survival (HR=4.63

95%

: 1.39~7.23;

=0.007) and disease-free survival (HR=5.82

95%

: 1.56~11.42;

=0.003). In the cell experiment

transfection with the miR-124 mimics significantly attenuated the proliferation of T24 cells (

0.05) and lowered the expressions of proliferation-related proteins (PCNA

Ki-67) and p-AKT as compared with the negative control (

0.05)

while transfection with the miR-124 inhibitor resulted in the reverse changes (

0.05).

Conclusion

The low expression of miR-124 in bladder cancer cells and tissues can promote cancer cell proliferation and is associated with a poor prognosis of the patients possibly in relation with the activation of AKT signaling pathway.

关键词

Keywords

references

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