title: Tristetraprolin inhibits the growth of human glioma cells through downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor mRNAs.
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.
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Nal Ae
authors.initials: NA
authors.lastname: Yoon
authors.affiliation: Department of Molecular Medicine, Gachon University of Medicine and Science, Incheon 406-840, Korea.
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Seokmin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Seong
authors.affiliation: Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology (KIT), Jinju 660-844, Korea.
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Physiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Korea.
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Paek
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-703, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D051816:Tristetraprolin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D055293:Receptors, Urokinase Plasminogen Activator; D051816:Tristetraprolin; D014568:Urokinase-Type Plasminogen Activator
keywords: TTP; glioma; uPA; uPAR