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Cancer Biol Ther. 2016 Oct 02;17(10):1070-1078. doi: 10.1080/15384047.2016.1219818. Epub 2016 Sep 16.

Downregulation of a novel human gene, ROGDI, increases radiosensitivity in cervical cancer cells.

Cancer biology & therapy

Yi-Fan Chen, Jonathan J Cho, Tsai-Hua Huang, Chao-Neng Tseng, Eng-Yen Huang, Chung-Lung Cho

Affiliations

  1. a Department of Biological Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan.
  2. b Department of Medicine , College of Medicine, University of Florida , MSB, Gainesville , FL , USA.
  3. c Division of Endocrinology & Metabolism , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Kaohsiung , Taiwan.
  4. d Department of Radiation Oncology , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Kaohsiung , Taiwan.

PMID: 27636029 PMCID: PMC5079390 DOI: 10.1080/15384047.2016.1219818

Abstract

ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation. Inhibition of cyclin-dependent kinases (CDKs) can lead to a halt of cell cycle progression and a stay at different phases or checkpoints. Our data show that the downregulation of ROGDI led to a decreased expression of CDK 1, 2, cyclin A, B and resulted in a G2/M phase transition block. In addition, the downregulation of ROGDI increased cell accumulation at the G2 phase as detected using flow cytometry and decreased cell survival as revealed by clonogenic assay in HeLa and C33A cells following irradiation. These findings suggest that the downregulation of ROGDI can mediate radiosensitivity by blocking cells at G2/M, the most radiosensitive phase of the cell cycle, as well as exerting deleterious effects in the form of DNA damage, as shown by increased γ-H2AX activation.

Keywords: DNA; ROGDI; cyclin-dependent kinases; damage; radiosensitivity; γ-H2AX

References

  1. Cancer Res. 2004 Oct 1;64(19):7144-9 - PubMed
  2. Chang Gung Med J. 2000 Jul;23(7):396-404 - PubMed
  3. PLoS One. 2011;6(7):e22879 - PubMed
  4. Mol Cell Biol. 1997 Sep;17(9):5588-97 - PubMed
  5. J Biol Chem. 2007 Jul 20;282(29):21206-12 - PubMed
  6. J Radiat Res. 2003 Dec;44(4):329-33 - PubMed
  7. Acta Oncol. 2007;46(5):628-38 - PubMed
  8. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e507-14 - PubMed
  9. Cell Death Dis. 2012 Jan 12;3:e251 - PubMed
  10. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5490-4 - PubMed
  11. Oncogene. 2000 Feb 3;19(5):649-60 - PubMed
  12. Mol Cancer Ther. 2008 Jul;7(7):1772-81 - PubMed
  13. Cancer Res. 2002 Dec 15;62(24):7316-27 - PubMed
  14. Nature. 1995 Jul 27;376(6538):313-20 - PubMed
  15. Int J Radiat Biol. 2008 Feb;84(2):151-64 - PubMed
  16. Oncogene. 2001 Aug 2;20(34):4601-12 - PubMed
  17. Science. 1998 May 15;280(5366):1089-91 - PubMed
  18. Mol Cell Biol. 2009 May;29(10):2828-40 - PubMed
  19. Cancer Res. 2007 Feb 1;67(3):1046-53 - PubMed
  20. Int J Radiat Biol. 2008 Apr;84(4):253-64 - PubMed
  21. Mol Cell. 2009 Jul 31;35(2):228-39 - PubMed
  22. Nat Cell Biol. 2002 Jan;4(1):11-9 - PubMed
  23. Br J Cancer. 2000 Aug;83(3):354-9 - PubMed
  24. Cell. 1994 Jul 15;78(1):59-66 - PubMed
  25. Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5501s-5508s - PubMed
  26. Cell. 1993 Nov 19;75(4):805-16 - PubMed
  27. Oral Health Dent Manag. 2014 Sep;13(3):728-30 - PubMed
  28. Mol Syndromol. 2014 Dec;5(6):293-8 - PubMed

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