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Enhanced anticancer effects of a methylation inhibitor by inhibiting a novel DNMT1 target, CEP 131, in cervical cancer

  • Kim, Dong Hyun (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Hye-Min (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Huong, Pham Thi Thu (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Han, Ho-Jin (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hwang, Joonsung (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Cha-Molstad, Hyunjoo (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Kyung Ho (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ryoo, In-Ja (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Kyoon Eon (Department of Biochemistry, College of Natural Science, Chungnam National University) ;
  • Huh, Yang Hoon (Center for Electron Microscopy Research, Korea Basic Science Institute) ;
  • Ahn, Jong Seog (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kwon, Yong Tae (Protein Metabolism Medical Research Center, Department of Biomedical Sciences, College of Medicine, Seoul National University) ;
  • Soung, Nak-Kyun (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Bo Yeon (Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2019.02.25
  • Accepted : 2019.04.09
  • Published : 2019.05.31

Abstract

Methylation is a primary epigenetic mechanism regulating gene expression. 5-aza-2'-deoxycytidine is an FDA-approved drug prescribed for treatment of cancer by inhibiting DNA-Methyl-Transferase 1 (DNMT1). Results of this study suggest that prolonged treatment with 5-aza-2'-deoxycytidine could induce centrosome abnormalities in cancer cells and that CEP131, a centrosome protein, is regulated by DNMT1. Interestingly, cancer cell growth was attenuated in vitro and in vivo by inhibiting the expression of Cep131. Finally, Cep131-deficient cells were more sensitive to treatment with DNMT1 inhibitors. These findings suggest that Cep131 is a potential novel anti-cancer target. Agents that can inhibit this protein may be useful alone or in combination with DNMT1 inhibitors to treat cancer.

Keywords

References

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