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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332028PMC
http://dx.doi.org/10.14348/molcells.2015.2259DOI Listing

Publication Analysis

Top Keywords

upa upar
20
human glioma
16
glioma cells
12
urokinase plasminogen
12
plasminogen activator
12
inhibits growth
8
cells downregulation
8
activator receptor
8
growth glioblastoma
8
overexpression ttp
8

Similar Publications

(Thio)chromenone derivatives exhibit anti-metastatic effects through selective inhibition of uPAR in cancer cell lines: discovery of an uPAR-targeting fluorescent probe.

Chem Commun (Camb)

January 2025

Center for Metareceptome Research, Graduate School of Pharmaceutical Sciences, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea.

A class of (thio)chromenone derivatives has been identified as suitable ligands for uPAR, a glycoprotein with a prognostic value in a large number of human cancers. The (thio)chromenone agents actively inhibited the binding of uPAR to uPA with a binding affinity of 18.6 nM, reducing cell migration in the wound healing assay by up to 40% without apparent cell motility.

View Article and Find Full Text PDF

Introduction: The plasminogen activating (PA) system has a multitude of functions such as wound healing, proteolytic activity, collagen degradation and cell growth, and the role of the urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) system has been studied in many disease states. The aim of this study was to investigate salivary concentrations of uPA, uPAR and uPA activity in patients with periodontitis to identify biomarkers and novel pathogenic relationships.

Methods: Saliva samples were obtained from 169 participants, comprising patients with periodontitis (n = 103) and periodontally healthy volunteers (n = 66) and analysed for uPA and uPAR with a multiplex protein assay using proximity extension analysis in a subset of samples, followed by validation with ELISA.

View Article and Find Full Text PDF

Novel targets for mucosal healing in inflammatory bowel disease therapy.

Int Immunopharmacol

January 2025

Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran. Electronic address:

Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis.

View Article and Find Full Text PDF

Male SARS-CoV-2-infected patients have higher hospitalization rates, ICU admissions, and mortality compared to females, yet with unclear underlying mechanisms. We investigated the influence of biological sex on COVID-19 severity and patient outcomes. We profiled 41 circulating host response markers and identified differentially regulated proteins based on disease severity using covariates, such as sex, age, BMI, diabetes, and corticosteroid administration.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!