title: 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.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wangbing
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Dingbo
authors.initials: D
authors.lastname: Shi
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Taihua
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Bilian
authors.initials: B
authors.lastname: Jin
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Deng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D019098:Telomerase / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C400219:RFPL3 protein, human; D019098:Telomerase