Oncotarget

Research Papers:

RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth

Yu Qin, Wangbing Chen, Yao Xiao, Wendan Yu, Xin Cai, Meng Dai, Tingting Xu, Wenlin Huang, Wei Guo, Wuguo Deng _ and Taihua Wu

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Oncotarget. 2015; 6:27130-27145. https://doi.org/10.18632/oncotarget.4825

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Abstract

Yu Qin1,*, Wangbing Chen2,3,*, Yao Xiao1,*, Wendan Yu1, Xin Cai1, Meng Dai1, Tingting Xu1, Wenlin Huang2,4, Wei Guo1, Wuguo Deng2,4, Taihua Wu1

1The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China

2Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China

3Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

4State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Wuguo Deng, e-mail: dengwg@sysucc.org.cn

Wei Guo, e-mail: wei1015@msn.com

Taihua Wu, e-mail: wutaihua@sina.com

Keywords: RFPL3, CBP, hTERT, lung cancer

Received: March 21, 2015     Accepted: July 30, 2015     Published: August 11, 2015

ABSTRACT

hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also found that RFPL3 coordinated with CBP to upregulate hTERT through the CBP-induced acetylation of RFPL3 protein and their co-anchoring at hTERT promoter region. Collectively, our results reveal a new mechanism of hTERT regulation in lung cancer cells and suggest the RFPL3/CBP/hTERT signaling pathway may be a new targets for lung cancer treatment.


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