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

被引:12
作者
Ryu, Jinhyun [1 ]
Yoon, Nal Ae [2 ]
Lee, Yeon Kyung [3 ]
Jeong, Joo Yeon [1 ]
Kang, Seokmin [1 ]
Seong, Hyemin [1 ]
Choi, Jungil [4 ]
Park, Nammi [5 ]
Kim, Nayoung [6 ]
Cho, Wha Ja [7 ]
Paek, Sun Ha [8 ]
Cho, Gyeong Jae [1 ]
Choi, Wan Sung [1 ]
Park, Jae-Yong [9 ]
Park, Jeong Woo [2 ]
Kang, Sang Soo [1 ]
机构
[1] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Anat & Convergence Med Sci, Jinju 660751, South Korea
[2] Univ Ulsan, Dept Biol Sci, Ulsan 680749, South Korea
[3] Gachon Univ Med & Sci, Dept Mol Med, Inchon 406840, South Korea
[4] KIT, Gyeongnam Dept Environm Toxicol & Chem, Jinju 660844, South Korea
[5] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Physiol, Jinju 660751, South Korea
[6] Asan Med Ctr, Asan Inst Life Sci, Seoul 138736, South Korea
[7] Univ Ulsan, Coll Med, Ulsan Univ Hosp, Biomed Res Ctr, Ulsan 682060, South Korea
[8] Seoul Natl Univ, Coll Med, Dept Neurosurg, Seoul 110744, South Korea
[9] Korea Univ, Coll Hlth Sci, Sch Biosyst & Biomed Sci, Seoul 136703, South Korea
基金
新加坡国家研究基金会;
关键词
glioma; TTP; uPA; uPAR; PROTEIN TRISTETRAPROLIN; TUMOR-GROWTH; COLON-CANCER; EXPRESSION; RICH; STABILITY; INVASIVENESS; GLIOBLASTOMA; INVASION; RESVERATROL;
D O I
10.14348/molcells.2015.2259
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:156 / 162
页数:7
相关论文
共 33 条
  • [1] miR-29a inhibition normalizes HuR over-expression and aberrant AU-rich mRNA stability in invasive cancer
    Al-Ahmadi, Wijdan
    Al-Ghamdi, Maha
    Al-Souhibani, Norah
    Khabar, Khalid S. A.
    [J]. JOURNAL OF PATHOLOGY, 2013, 230 (01) : 28 - 38
  • [2] The RNA-binding zinc-finger protein tristetraprolin regulates AU-rich mRNAs involved in breast cancer-related processes
    Al-Souhibani, N.
    Al-Ahmadi, W.
    Hesketh, J. E.
    Blackshear, P. J.
    Khabar, K. S. A.
    [J]. ONCOGENE, 2010, 29 (29) : 4205 - 4215
  • [3] The plasminogen activation system in tumor growth, invasion, and metastasis
    Andreasen, PA
    Egelund, R
    Petersen, HH
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2000, 57 (01) : 25 - 40
  • [4] Post-transcriptional regulation in cancer
    Audic, Y
    Hartley, RS
    [J]. BIOLOGY OF THE CELL, 2004, 96 (07) : 479 - 498
  • [5] ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins
    Bakheet, T
    Frevel, M
    Williams, BRG
    Greer, W
    Khabar, KSA
    [J]. NUCLEIC ACIDS RESEARCH, 2001, 29 (01) : 246 - 254
  • [6] TIS11 Family Proteins and Their Roles in Posttranscriptional Gene Regulation
    Baou, Maria
    Jewell, Andrew
    Murphy, John J.
    [J]. JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2009,
  • [7] AU-rich elements and associated factors: are there unifying principles?
    Barreau, C
    Paillard, L
    Osborne, HB
    [J]. NUCLEIC ACIDS RESEARCH, 2005, 33 (22) : 7138 - 7150
  • [8] The mRNA-Destabilizing Protein Tristetraprolin Is Suppressed in Many Cancers, Altering Tumorigenic Phenotypes and Patient Prognosis
    Brennan, Sarah E.
    Kuwano, Yuki
    Alkharouf, Nadim
    Blackshear, Perry J.
    Gorospe, Myriam
    Wilson, Gerald M.
    [J]. CANCER RESEARCH, 2009, 69 (12) : 5168 - 5176
  • [9] Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways
    Brook, M
    Tchen, CR
    Santalucia, T
    McIlrath, J
    Arthur, JSC
    Saklatvala, J
    Clark, AR
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (06) : 2408 - 2418
  • [10] Expression, purification, and biochemical characterization of the antiinflammatory tristetraprolin: A zinc-dependent mRNA binding protein affected by posttranslational modifications
    Cao, HP
    [J]. BIOCHEMISTRY, 2004, 43 (43) : 13724 - 13738