title: RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth.
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.
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Yu
authors: Y
authors: Qin
authors: 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: Wangbing
authors: W
authors: Chen
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Yao
authors: Y
authors: Xiao
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Wendan
authors: W
authors: Yu
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Xin
authors: X
authors: Cai
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Meng
authors: M
authors: Dai
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Tingting
authors: T
authors: Xu
authors: 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: Wenlin
authors: W
authors: Huang
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Wei
authors: W
authors: Guo
authors: 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: Wuguo
authors: W
authors: Deng
authors: The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Taihua
authors: T
authors: Wu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D010446:Peptide Fragments; C400219:RFPL3 protein, human; D034741:RNA, Small Interfering; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; C509186:TERT protein, human; D019098:Telomerase
keywords: CBP; RFPL3; hTERT; lung cancer