Oncotarget

Research Papers:

A polymorphism in JMJD2C alters the cleavage by caspase-3 and the prognosis of human breast cancer

Qi Hong _, Sanjian Yu, Yu Yang, Guangyu Liu and Zhiming Shao

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Oncotarget. 2014; 5:4779-4787. https://doi.org/10.18632/oncotarget.2029

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Abstract

Qi Hong1,2,*, Sanjian Yu1,*, Yu Yang1,3,*, Guangyu Liu1 and Zhiming Shao1,2

1 Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, shanghai, China

2 Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China

3 School of basic medical sciences, Chengdu University of traditional Chinese medicine, Chengdu, P.R. China

* These authors contributed equally to this work

Correspondence:

Zhiming Shao, email:

Keywords: polymorphism, JMJD2C, caspase-3, cleavage, breast cancer

Received: April 2, 2014 Accepted: May 27, 2014 Published: May 27, 2014

Abstract

JMJD2C is a candidate oncogene that encodes a histone lysine demethylase with the ability to demethylate the lysine 9 residue of histone H3 (H3K9). The expression levels of JMJD2C are associated with tumor development and clinical outcome. Here we identify JMJD2C as a new substrate for caspase-3. JMJD2C is cleaved by caspase-3 at DEVD396G motif and then loses its demethylase activity. Additionally, we uncover D396N polymorphism (rs2296067) in the cleavage site of JMJD2C and establish its influence on the resistant to the cleavage by caspase-3. Importantly, we determined that D396N polymorphism is significantly associated with the prognosis of human breast cancer. We further found that the basal levels of DSB (double strand DNA break) repair proteins γ-H2AX (gamma-H2AX) increased when cells were treated with tumor necrosis factor-α (TNF-α) which activates caspase-3 activity. We also show that knockdown of JMJD2C expression results in up-regulation of basal γ-H2AX. We propose that D396N polymorphism of JMJD2C affects the prognosis of human breast cancer via altering the cleavage by caspase-3 and the ability of DSB repair which may contribute to therapy resistance.


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