Abstract
Abstract Malignant gliomas are one of the most common primary intrinsic brain tumors. In particular, glioblastoma multiforme (GBM), WHO grade IV, is highly invasive. Because of its high invasiveness, patients with unresectable GBM have a poor prognosis and have median survival of only a few months. The invasiveness of glioma depends on proteolysis of the extracellular matrix, a complex event occurring through the surrounding tissue during tumor cell invasion. Urokinase plasminogen activator (uPA) and its specific receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Tristetraprolin (TTP or ZFP36) is a tandem CCCH zinc-finger RNA-binding protein that regulates the stability of certain AU-rich element (ARE) mRNAs. Recent work reports that TTP is deficient in many cancer cells when compared with normal cell types. Moreover, the lack of TTP is associated with a variety of cancer-related processes. In the present study, we investigated the post-transcriptional regulation of uPA/uPAR expression by the tristetraprolin (TTP) in U87MG human glioma cells. Here, we showed that the overexpression of TTP decreased the stability of uPA/uPAR mRNA and the expression level of uPA/uPAR protein. uPA/uPAR mRNA include AU-rich elements (AREs) within the 3’-untranslated region, and TTP destabilized a luciferase mRNA containing uPA/uPAR AREs. In addition, TTP inhibits cell invasion in U87MG glioma cells. Present study demonstrates that TTP suppress the progression of glioma through the regulation of uPA/uPAR mRNA stability. Citation Format: Jinhyun Ryu, Jungil Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Gyeong Jae Cho, Wan Sung Choi, Jae-Yong Park, Jeong Woo Park, Sang Soo Kang. Tristetraprolin controls the stability of uPA/uPAR mRNA through binding to the 3’UTR of uPA/uPAR mRNA in U87MG glioma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3194. doi:10.1158/1538-7445.AM2013-3194
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