Oncotarget

Research Papers:

UBE2D3 gene overexpression increases radiosensitivity of EC109 esophageal cancer cells in vitro and in vivo

Xiaojia Gao, Wenbo Wang, Hui Yang, Lin Wu, Zhongshi He, Shuliang Zhou, Hong Zhao, Zhenming Fu, Fuxiang Zhou and Yunfeng Zhou _

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Oncotarget. 2016; 7:32543-32553. https://doi.org/10.18632/oncotarget.8869

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Abstract

Xiaojia Gao1,2,3,*, Wenbo Wang2,3,*, Hui Yang1,2,3, Lin Wu1,2,3, Zhongshi He1,2,3, Shuliang Zhou1,2,3, Hong Zhao1,2,3, Zhenming Fu2,3, Fuxiang Zhou2,3, Yunfeng Zhou2,3

1Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China

2Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China

3Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China

*These authors contributed equally to this work

Correspondence to:

Fuxiang Zhou, email: happyzhoufx@sina.com

Yunfeng Zhou, email: yfzhouwhu@163.com

Keywords: UBE2D3, ubiquitin, hTERT, radiosensitivity, esophageal cancer

Received: January 19, 2016     Accepted: March 31, 2016     Published: April 20, 2016

ABSTRACT

Ubiquitin-conjugating enzyme E2D3 (UBE2D3), a key component in ubiquitin (Ub) proteasome system, plays a crucial role in tumorigenesis. We previously found that it is bound to hTERT, and UBE2D3 could attenuate radiosensitivity of human breast cancer cells. Here we investigated a contributing role of UBE2D3 in radiosensitivity of esophageal squamous carcinoma. We demonstrated that the overexpression of UBE2D3 in esophageal squamous carcinoma cells (EC109) resulted in prolonged G1 phase and shortened G2/M phase after irradiation. UBE2D3 overexpression also decreased length of telomere and activity of telomerase. In addition, the overexpression of UBE2D3 increased mRNA expression but decreased protein levels of hTERT in both vitro and vivo systems. Compared with untreated cells, the treatment of UBE2D3 overexpressing cells with the specific proteasome inhibitor (MG132) could up-regulate hTERT. MG132 treatment of UBE2D3 overexpressed cells caused a clear and dramatic increase in the amount of ubiquitinated hTERT species. These findings indicate that UBE2D3 enhances radiosensitivity of EC109 cells by degradating hTERT through the ubiquitin proteolysis pathway.


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