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

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.
Authors	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, Wuguo Deng
Journal	Oncotarget (Oncotarget) Vol. 5 Issue 23 Pg. 11909-23 (Dec 15 2014) ISSN: 1949-2553 [Electronic] United States
PMID	25481043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins RFPL3 protein, human Telomerase
Topics	Animals Blotting, Western Carcinoma, Non-Small-Cell Lung (metabolism, mortality, pathology) Carrier Proteins (metabolism) Cell Line, Tumor Chromatin Immunoprecipitation Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Neoplastic (physiology) Heterografts Humans Immunohistochemistry Kaplan-Meier Estimate Lung Neoplasms (metabolism, mortality, pathology) Mice Mice, Nude Polymerase Chain Reaction Proportional Hazards Models Telomerase (biosynthesis) Tissue Array Analysis Transfection

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