Yuhong Chen1,2,3,4, Zhihui Dou1,2,3,4, Xiaohua Chen1,2,3,4, Dapeng Zhao1,2,3,4, Tuanjie Che5,6, Wei Su1,2,3,4, Tao Qu7, Taotao Zhang1,2,3,4, Caipeng Xu1,2,3,4, Huiweng Lei1,2,3,4, Qiang Li8,9,10,11,12, Hong Zhang13,14,15,16,17, Cuixia Di18,19,20,21,22. 1. Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. 2. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China. 3. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100039, China. 4. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100039, China. 5. Laboratory of Precision Medicine and Translational Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou Science and Technology Town Hospital, Suzhou, 215153, China. 6. Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, Lanzhou, 730030, China. 7. Department of Biotherapy Center, Gansu Provincial Hospital, Lanzhou, Gansu, China. 8. Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. liqiang@impcas.ac.cn. 9. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China. liqiang@impcas.ac.cn. 10. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100039, China. liqiang@impcas.ac.cn. 11. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100039, China. liqiang@impcas.ac.cn. 12. Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. liqiang@impcas.ac.cn. 13. Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. zhangh@impcas.ac.cn. 14. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China. zhangh@impcas.ac.cn. 15. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100039, China. zhangh@impcas.ac.cn. 16. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100039, China. zhangh@impcas.ac.cn. 17. Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. zhangh@impcas.ac.cn. 18. Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. dicx@impcas.ac.cn. 19. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China. dicx@impcas.ac.cn. 20. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100039, China. dicx@impcas.ac.cn. 21. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100039, China. dicx@impcas.ac.cn. 22. Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. dicx@impcas.ac.cn.
Abstract
PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.
PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.
Authors: Laura C Gomez; Mayra L Sottile; Martin E Guerrero-Gimenez; Felipe C M Zoppino; Analia L Redondo; Francisco E Gago; Javier I Orozco; Olga M Tello; Maria Roqué; Silvina B Nadin; Diego M Marzese; Laura M Vargas-Roig Journal: J Clin Pathol Date: 2017-07-25 Impact factor: 3.411
Authors: Nikola Holtkamp; Isis Atallah; Ali-Fuat Okuducu; Jana Mucha; Christian Hartmann; Victor-F Mautner; Reinhard E Friedrich; Christian Mawrin; Andreas von Deimling Journal: Neoplasia Date: 2007-08 Impact factor: 5.715