Oncotarget

Research Papers:

Ret finger protein-like 3 promotes tumor cell growth by activating telomerase reverse transcriptase expression in human lung cancer cells

Wangbing Chen _, Jianjun Lu, Yu Qin, Jingshu Wang, Yun Tian, Dingbo Shi, Shusen Wang, Yao Xiao, Meng Dai, Lu Liu, Guo Wei, Taihua Wu, Bilian Jin, Xiangsheng Xiao, Tie-Bang Kang, Wenlin Huang and Wuguo Deng

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Oncotarget. 2014; 5:11909-11923. https://doi.org/10.18632/oncotarget.2557

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Abstract

Wangbing Chen1,4,*, Jianjun Lu3,*, Yu Qin2,*, Jingshu Wang1,*, Yun Tian1, Dingbo Shi1, Shusen Wang1, Yao Xiao2, Meng Dai2, Lu Liu2, Guo Wei2, Taihua Wu2, Bilian Jin2, Xiangsheng Xiao1, Tie-Bang Kang1, Wenlin Huang1,5, Wuguo Deng1,5

1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China

2Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China

3Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

5State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China

*These authors contributed equally to this article

Correspondence to:

Shusen Wang, e-mail: [email protected]

Bilian Jin, e-mail: [email protected]

Wuguo Deng, e-mail: [email protected]

Received: August 10, 2014     Accepted: October 01, 2014     Published: November 13, 2014

ABSTRACT

In this study, we identified ret finger protein-like 3 (RFPL3) as a hTERT promoter binding protein in lung cancer cells. The high hTERT promoter-binding activity of RFPL3 was detected in lung cancer cells compared to normal cells. Chromatin immunoprecipitation confirmed RFPL3 as a tumor-specific hTERT promoter binding protein. Overexpression of RFPL3 activated hTERT promoter and up-regulated hTERT expression and telomerase activity. Inhibition of RFPL3 expression by siRNA suppressed hTERT promoter activation and telomerase activity. Inhibition of RFPL3 by siRNA or shRNA also significantly inhibited tumor cell growth in vitro and in a xenograft mouse model in vivo. Immunohistochemical analysis of 181 human lung adenocarcinomas specimens showed a significant correlation between RFPL3 and hTERT expression. The overexpression of RFPL3 was also associated significantly with lymph node metastasis. Univariate and multivariate Cox model analyses of NSCLC clinical specimens revealed a strong correlation between RFPL3 expression and overall survival. These results demonstrate that RFPL3 is an important cellular factor which promotes lung cancer growth by activating hTERT expression and may be a potential novel therapeutic target for lung cancer.


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