Effect of RRM2 on proliferation and invasion of bladder cancer cells

Haibin LI; Sen GAO

doi:10.16016/j.1000-5404.202103137

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Effect of RRM2 on proliferation and invasion of bladder cancer cells

Basic Medicine | 更新时间：2026-01-09

- Effect of RRM2 on proliferation and invasion of bladder cancer cells
- Journal of Third Military Medical University Vol. 43, Issue 18, Pages: 1762-1768(2021)
- 作者机构：
  
  100029 北京，北京中医药大学第三附属医院泌尿外科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202103137
  CLC： R345;R730.23;R737.14
- Received：16 March 2021，
  
  Revised：2021-06-16，
  
  Published：30 September 2021
- 稿件说明：
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Haibin LI, Sen GAO. Effect of RRM2 on proliferation and invasion of bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(18): 1762-1768.
DOI：

Haibin LI, Sen GAO. Effect of RRM2 on proliferation and invasion of bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(18): 1762-1768. DOI： 10.16016/j.1000-5404.202103137.

摘要

目的

探讨核糖核苷酸还原酶调节亚基M2(ribonucleotide reductase regulatory subunit M2，RRM2)在膀胱癌细胞中的生物学功能及其机制。

方法

采用TCGA及Oncomine数据库分析膀胱癌患者RRM2的表达，生存分析采用K-M Plot在线分析网站。收集2019年6月至2020年12月在本院泌尿外科手术患者的膀胱癌组织和癌旁组织，通过qRT-PCR检测其RRM2的表达情况。采用膀胱癌细胞系(5637、T24、Ej、BIU-87)进行细胞实验；选取高表达RRM2的细胞进行沉默实验，采用CCK-8、Transwell检测RRM2对膀胱癌细胞增殖、侵袭的影响，Western blot检测wnt/β-catenin信号通路相关蛋白的表达。

结果

RRM2在膀胱癌患者中表达升高(差异表达倍数Log

FC= 4.546

0.01)，高表达的RRM2与患者不良预后及较差的总体生存率相关。体外细胞实验显示，与5637和T24细胞相比，siRNA转染沉默RRM2后72、96 h显著抑制膀胱癌细胞的增殖(

0.01)；并显著减弱膀胱癌细胞的侵袭能力(

0.01)。沉默RRM2后，总β-catenin表达水平显著降低，Wnt/β-catenin信号通路的下游蛋白，包括在肿瘤进展中起重要作用的细胞周期蛋白D1和c-Myc也显著降低。

结论

RRM2可促进膀胱癌细胞的增殖和侵袭，可能靶向wnt/β-catenin通路发挥促癌作用。

Abstract

Objective

To explore the biological function and mechanism of ribonucleotide reductase regulatory subunit M2 (RRM2) in bladder cancer cells.

Methods

The Cancer Genome Atlas (TCGA) and Oncomine databases were used to analyze the expression of RRM2 in patients with bladder cancer

and the K-M Plot online analysis was used for survival analysis. The bladder cancer tissues and adjacent tissues from the patients undergoing urological surgery in our hospital from June 2019 to December 2020 were collected and detected for the expression of RRM2 by qRT-PCR. CCK-8 and Transwell assays were employed to evaluate the effects of RRM2 on proliferation and invasion in bladder cancer cell lines (5637

T24

Ej and BIU-87 cells). Then the effect of RRM2 silence was determined with CCK-8 and Transwell assays in the cells with higher expression of RRM2

and the expression levels of Wnt/β-catenin signaling pathway related proteins were measured with Western blotting.

Results

The expression of RRM2 was increased in patients with bladder cancer (differential expression multiple Log

FC=4.546

0.01)

and the patients with high expression of RRM2 were associated with poor prognosis and poor overall survival.

In vitro

cell experiments showed that RRM2 silence significantly inhibited the proliferation and reduced the invasion of bladder cancer RRM2 cells in 72 and 96 h after siRNA transfection when compared with the 5637 and T24 cells (

0.01). The silence also significantly decreased the expression levels of total β-catenin and Wnt/β-catenin downstream proteins cyclin D1 and c-myc

which played important roles in tumor progression.

Conclusion

RRM2 can promote the proliferation and invasion of bladder cancer cells

and may target the Wnt/β-catenin pathway to promote bladder cancer.

关键词

Keywords

references

SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2015 [J]. CA Cancer J Clin, 2015, 65(1): 5-29. DOI: 10.3322/caac.21254.

KARAKIEWICZ P I, BENAYOUN S, ZIPPE C, et al . Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder[J ] . BJU Int, 2006, 97(5): 997-1001. DOI: 10.1111/j.1464-410X.2006.06036.x.

CLARK P E, AGARWAL N, BIAGIOLI M C, et al . Bladder cancer [J ] . J Natl Compr Canc Netw, 2013, 11(4): 446-475.

BOLENZ C, LOTAN Y. Molecular biomarkers for urothelial carcinoma of the bladder: challenges in clinical use[J]. Nat Clin Pract Urol, 2008, 5(12): 676-685. DOI: 10.1038/ncpuro1259.

LI C, ZHENG J, CHEN S, et al . RRM2 promotes the progression of human glioblastoma[J ] . J Cell Physiol, 2018, 233(10): 6759-6767. DOI: 10.1002/jcp.26529.

MAZZU Y Z, ARMENIA J, CHAKRABORTY G, et al . A novel mechanism driving poor-prognosis prostate cancer: overexpression of the DNA repair gene, ribonucleotide reductase small subunit M2 (RRM2)[J ] . Clin Cancer Res, 2019, 25(14): 4480-4492. DOI: 10.1158/1078-0432.CCR-18-4046.

QUAN D L, CHEN K, ZHANG J R, et al . Identification of lncRNA NEAT1/miR-21/RRM2 axis as a novel biomarker in breast cancer[J ] . J Cell Physiol, 2020, 235(4): 3372-3381. DOI: 10.1002/jcp.29225.

SANCHEZ-CARBAYO M, SOCCI N D, LOZANO J, et al . Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays[J ] . J Clin Oncol, 2006, 24(5): 778-789. DOI: 10.1200/JCO.2005.03.2375.

MORIKAWA T, MAEDA D, KUME H, et al . Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer[J ] . Histopathology, 2010, 57(6): 885-892. DOI: 10.1111/j.1365-2559.2010.03725.x.

CHEN W X, YANG L G, XU L Y, et al . Bioinformatics analysis revealing prognostic significance ofRRM2 gene in breast cancer[J ] . Biosci Rep, 2019, 39(4): BSR20182062. DOI: 10.1042/BSR20182062.

SACK L M, DAVOLI T, LI M Z, et al . Profound tissue specificity in proliferation control underlies cancer drivers and aneuploidy patterns[J ] . Cell, 2018, 173(2): 499-514.e23. DOI: 10.1016/j.cell.2018.02.037.

SUN H, YANG B, ZHANG H, et al . RRM2 is a potential prognostic biomarker with functional significance in glioma[J ] . Int J Biol Sci, 2019, 15(3): 533-543. DOI: 10.7150/ijbs.30114.

ZHUANG S J, LI L, ZANG Y W, et al . RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling[J ] . Oncol Lett, 2020, 19(4): 3349-3355. DOI: 10.3892/ol.2020.11428.

REN L L, CHEN H, SONG J W, et al . MiR-454-3p-mediated wnt/β-catenin signaling antagonists suppression promotes breast cancer metastasis[J ] . Theranostics, 2019, 9(2): 449-465. DOI: 10.7150/thno.29055.

YUE X, LAN F, XIA T. Hypoxicglioma cell-secreted exosomal miR-301a activates wnt/β-catenin signaling and promotes radiation resistance by targeting TCEAL7[J]. Mol Ther, 2019, 27(11): 1939-1949. DOI: 10.1016/j.ymthe.2019.07.011.

REN R, YU J, ZHANG Y, et al . Inflammation promotes progression of pancreatic cancer through WNT/β-catenin pathway-dependent manner[J ] . Pancreas, 2019, 48(8): 1003-1014. DOI: 10.1097/MPA.0000000000001386.

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