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Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

  • Ryu, Jinhyun (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Yoon, Nal Ae (Department of Biological Sciences, University of Ulsan) ;
  • Lee, Yeon Kyung (Department of Molecular Medicine, Gachon University of Medicine and Science) ;
  • Jeong, Joo Yeon (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Kang, Seokmin (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Seong, Hyemin (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Choi, Jungil (Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology (KIT)) ;
  • Park, Nammi (Department of Physiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Kim, Nayoung (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Cho, Wha Ja (Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine) ;
  • Paek, Sun Ha (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Cho, Gyeong Jae (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Choi, Wan Sung (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University) ;
  • Park, Jae-Yong (School of Biosystem and Biomedical Science, College of Health Science, Korea University) ;
  • Park, Jeong Woo (Department of Biological Sciences, University of Ulsan) ;
  • Kang, Sang Soo (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
  • Received : 2014.09.25
  • Accepted : 2014.10.30
  • Published : 2015.02.28

Abstract

Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

Keywords

References

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