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http://dx.doi.org/10.14348/molcells.2015.2259

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)
Publication Information
Molecules and Cells / v.38, no.2, 2015 , pp. 156-162 More about this Journal
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
glioma; TTP; uPA; uPAR;
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1 Kleihues, P., Soylemezoglu, F., Schauble, B., Scheithauer, B.W., and Burger, P.C. (1995). Histopathology, classification, and grading of gliomas. Glia 15, 211-221.   DOI
2 Ku, B.M., Lee, Y.K., Jeong, J.Y., Ryu, J., Choi, J., Kim, J.S., Cho, Y.W., Roh, G.S., Kim, H.J., Cho, G.J., et al. (2011). Caffeine inhibits cell proliferation and regulates PKA/GSK3beta pathways in U87MG human glioma cells. Mol. Cells 31, 275-279.   DOI   ScienceOn
3 Lee, H.H., Son, Y.J., Lee, W.H., Park, Y.W., Chae, S.W., Cho, W.J., Kim, Y.M., Choi, H.J., Choi, D.H., Jung, S.W., et al. (2010a). Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer. Int. J. Cancer 126, 1817-1827.   DOI
4 Lee, H.H., Vo, M.T., Kim, H.J., Lee, U.H., Kim, C.W., Kim, H.K., Ko, M.S., Lee, W.H., Cha, S.J., Min, Y.J., et al. (2010b). Stability of the LATS2 tumor suppressor gene is regulated by tristetraprolin. J. Biol. Chem. 285, 17329-17337.   DOI   ScienceOn
5 Lee, H.H., Yang, S.S., Vo, M.T., Cho, W.J., Lee, B.J., Leem, S.H., Lee, S.H., Cha, H.J., and Park, J.W. (2013). Tristetraprolin down-regulates IL-23 expression in colon cancer cells. Mol. Cells 36, 571-576.   DOI
6 Lykke-Andersen, J., and Wagner, E. (2005). Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes Dev. 19, 351-361.   DOI   ScienceOn
7 Marderosian, M., Sharma, A., Funk, A.P., Vartanian, R., Masri, J., Jo, O.D., and Gera, J.F. (2006). Tristetraprolin regulates cyclin D1 and c-Myc mRNA stability in response to rapamycin in an Akt-dependent manner via p38 MAPK signaling. Oncogene 25, 6277-6290.   DOI   ScienceOn
8 Nanbu, R., Menoud, P.A., and Nagamine, Y. (1994). Multiple instability-regulating sites in the 3' untranslated region of the urokinase-type plasminogen activator mRNA. Mol. Cell. Biol. 14, 4920-4928.   DOI
9 Al-Ahmadi, W., Al-Ghamdi, M., Al-Souhibani, N., and Khabar, K.S. (2013). miR-29a inhibition normalizes HuR over-expression and aberrant AU-rich mRNA stability in invasive cancer. J. Pathol. 230, 28-38.   DOI   ScienceOn
10 Al-Souhibani, N., Al-Ahmadi, W., Hesketh, J.E., Blackshear, P.J., and Khabar, K.S. (2010). The RNA-binding zinc-finger protein tristetraprolin regulates AU-rich mRNAs involved in breast cancer-related processes. Oncogene 29, 4205-4215.   DOI   ScienceOn
11 Andreasen, P.A., Egelund, R., and Petersen, H.H. (2000). The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol. Life Sci. 57, 25-40.   DOI
12 Audic, Y., and Hartley, R. (2004). Post-transcriptional regulation in cancer. Biol. Cell 96, 479-498.   DOI   ScienceOn
13 Bakheet, T., Frevel, M., Williams, B.R., Greer, W., and Khabar, K.S. (2001). ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic Acids Res. 29, 246-254.   DOI   ScienceOn
14 Baou, M., Jewell, A., and Murphy, J.J. (2009). TIS11 family proteins and their roles in posttranscriptional gene regulation. J. Biomed. Biotechnol. 2009, 634520.
15 Barreau, C., Paillard, L., and Osborne, H.B. (2005). AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Res. 33, 7138-7150.   DOI   ScienceOn
16 Brennan, S.E., Kuwano, Y., Alkharouf, N., Blackshear, P.J., Gorospe, M., and Wilson, G.M. (2009). The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis. Cancer Res. 69, 5168-5176.   DOI   ScienceOn
17 Ryu, J., Ku, B.M., Lee, Y.K., Jeong, J.Y., Kang, S., Choi, J., Yang, Y., Lee, D.H., Roh, G.S., Kim, H.J., et al. (2011). Resveratrol reduces TNF-alpha-induced U373MG human glioma cell invasion through regulating NF-kappaB activation and uPA/uPAR expression. Anticancer Res. 31, 4223-4230.
18 Park, J.Y., Hwang, E.M., Park, N., Kim, E., Kim, D.G., Kang, D., Han, J., Choi, W.S., Ryu, P.D., and Hong, S.G. (2007). Gateway RFP-fusion vectors for high throughput functional analysis of genes. Mol. Cells 23, 357-362.
19 Rao, J.S. (2003). Molecular mechanisms of glioma invasiveness: the role of proteases. Nat. Rev. Cancer 3, 489-501.   DOI   ScienceOn
20 Roldan, A.L., Cubellis, M.V., Masucci, M.T., Behrendt, N., Lund, L.R., Dano, K., Appella, E., and Blasi, F. (1990). Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. 9, 467-474.
21 Sehgal, A. (1998). Molecular changes during the genesis of human gliomas. Semin. Surg. Oncol. 14, 3-12.   DOI
22 Selmi, T., Martello, A., Vignudelli, T., Ferrari, E., Grande, A., Gemelli, C., Salomoni, P., Ferrari, S., and Zanocco-Marani, T. (2012). ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways. Cell Cycle 11, 1977-1987.   DOI   ScienceOn
23 Stoecklin, G., Gross, B., Ming, X.F., and Moroni, C. (2003). A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA. Oncogene 22, 3554-3561.   DOI   ScienceOn
24 Suswam, E., Li, Y., Zhang, X., Gillespie, G.Y., Li, X., Shacka, J.J., Lu, L., Zheng, L., and King, P.H. (2008). Tristetraprolin downregulates interleukin-8 and vascular endothelial growth factor in malignant glioma cells. Cancer Res. 68, 674-682.   DOI   ScienceOn
25 Gagliano, N., Moscheni, C., Torri, C., Magnani, I., Bertelli, A.A., and Gioia, M. (2005). Effect of resveratrol on matrix metalloproteinase- 2 (MMP-2) and secreted protein acidic and rich in cysteine (SPARC) on human cultured glioblastoma cells. Biomed. Pharmacother. 59, 359-364.   DOI   ScienceOn
26 Brook, M., Tchen, C.R., Santalucia, T., McIlrath, J., Arthur, J.S., Saklatvala, J., and Clark, A.R. (2006). Posttranslational regulation of triste-traprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signalregulated kinase pathways. Mol. Cell. Biol. 26, 2408-2418.   DOI   ScienceOn
27 Cao, H. (2004). Expression, purification, and biochemical characterization of the antiinflammatory tristetraprolin: a zinc-dependent mRNA binding protein affected by posttranslational modifications. Biochemistry 43, 13724-13738.   DOI   ScienceOn
28 Ellis, V., and Dano, K. (1993). Potentiation of plasminogen activation by an anti-urokinase monoclonal antibody due to ternary complex formation. A mechanistic model for receptor-mediated plasminogen activation. J. Biol. Chem. 268, 4806-4813.
29 Gladson, C.L., Pijuan-Thompson, V., Olman, M.A., Gillespie, G.Y., and Yacoub, I.Z. (1995). Up-regulation of urokinase and urokinase receptor genes in malignant astrocytoma. Am. J. Pathol. 146, 1150-1160.
30 Gondi, C.S., Lakka, S.S., Dinh, D.H., Olivero, W.C., Gujrati, M., and Rao, J.S. (2004). Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growth. Neuron Glia Biol. 1, 165-176.   DOI
31 Gruber, A.R., Fallmann, J., Kratochvill, F., Kovarik, P., and Hofacker, I.L. (2011). AREsite: a database for the comprehensive investigation of AU-rich elements. Nucleic Acids Res. 39, D66-69.
32 Yamamoto, M., Ueno, Y., Hayashi, S., and Fukushima, T. (2002). The role of proteolysis in tumor invasiveness in glioblastoma and metastatic brain tumors. Anticancer Res. 22, 4265-4268.
33 Ulisse, S., Baldini, E., Sorrenti, S., and D'Armiento, M. (2009). The urokinase plasminogen activator system: a target for anti-cancer therapy. Curr. Cancer Drug Targets 9, 32-71.   DOI   ScienceOn