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Breast Cancer Research
Published in: Breast Cancer Research 3/2014

Open Access 01-06-2014 | Research article

JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI

Authors: Li-Liang Li, Ai-Min Xue, Bei-Xu Li, Yi-Wen Shen, Yu-Hua Li, Cheng-Liang Luo, Ming-Chang Zhang, Jie-Qing Jiang, Zu-De Xu, Jian-Hui Xie, Zi-Qin Zhao

Published in: Breast Cancer Research | Issue 3/2014

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Abstract

Introduction

Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression through transcriptional repression of the tumor suppressor aplasia Ras homolog member I (ARHI).

Methods

Immunohistochemistry was performed to examine protein expressions in 155 cases of breast cancer and 30 non-neoplastic tissues. Spearman correlation analysis was used to analyze the correlation between JMJD2A expression and clinical parameters as well as several tumor regulators in 155 cases of breast cancer. Gene and protein expressions were monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Results from knockdown of JMJD2A, overexpression of JMJD2A, Co-immunoprecipitation (Co-IP) assay, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) elucidated molecular mechanisms of JMJD2A action in breast cancer progression. Furthermore, the effects of ARHI overexpression on JMJD2A-mediated tumor progression were investigated in vitro and in vivo. For in vitro experiments, cell proliferation, wound-healing, migration and invasion were monitored by cell counting, scratch and Boyden Chamber assays. For in vivo experiments, control cells and cells stably expressing JMJD2A alone or together with ARHI were inoculated into mammary fat pads of mice. Tumor volume, tumor weight and metastatic nodules were measured by caliper, electronic balance and nodule counting, respectively.

Results

JMJD2A was highly expressed in human breast cancers and positively correlated with tumor progression. Knockdown of JMJD2A increased ARHI expression whereas overexpression of JMJD2A decreased ARHI expression at both protein and mRNA levels. Furthermore, E2Fs and histone deacetylases were involved in the transcriptional repression of ARHI expression by JMJD2A. And the aggressive behavior of JMJD2A in breast cancers could be reversed by re-expression of ARHI in vitro and in vivo.

Conclusion

We demonstrated a cancer-promoting effect of JMJD2A and defined a novel molecular pathway contributing to JMJD2A-mediated breast cancer progression.
Appendix
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Metadata
Title
JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI
Authors
Li-Liang Li
Ai-Min Xue
Bei-Xu Li
Yi-Wen Shen
Yu-Hua Li
Cheng-Liang Luo
Ming-Chang Zhang
Jie-Qing Jiang
Zu-De Xu
Jian-Hui Xie
Zi-Qin Zhao
Publication date
01-06-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3667

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