scription, cell cycle progression and apoptosis by altering the function and/or stability of target proteins (5). Pin1 induces conformational changes in its target phospho-proteins by binding and isomerizing the peptidyl-prolyl bond in phos-

Glioblastoma is the most common and most aggressive type of primary brain tumor. Current approaches in the treatment of glioblastoma are not effective enough to increase patient survival or prevent recurrence following surgery. Consequently, the search for potential drug targets is ongoing. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1), an isomerase that is overexpressed in various tumors, has become an attractive molecule in cancer research. Pin1 has been reported to regulate proteins involved in essential cellular pathways that mediate cell proliferation, cell cycle progression, differentiation and apoptosis, by altering their stability and function. The results of the present study revealed that knockdown of Pin1 in glioblastoma cells using RNA interference or the selective Pin1 inhibitor, juglone, suppressed the tumorigenic features by reducing cell growth, migration and angiogenic potential. Furthermore, knockdown of Pin1 decreased the levels of vascular endothelial growth factor and matrix metallopeptidase 9, and also triggered apoptosis. Due to the fundamental roles of Pin1 in promoting tumorigenesis, Pin1 inhibitory molecules, including juglone, or alternative synthetic derivatives hold potential for the development of clinical countermeasures against glioblastoma. Introduction Glioblastoma is the most common and most aggressive type of primary brain tumor, accounting for nearly 65% of all primary intracranial tumors and conferring a median survival time of ~14 months (1). The molecular mechanisms underlying the pathology of glioblastoma, which is not completely curable by means of chemotherapy, radiotherapy and surgery, are yet to be fully elucidated. Therefore, the search for candidate molecules to be employed as countermeasures against glioblastoma remains essential. In addition, it is equally important to identify potential target molecules responsible for the pathogenesis of glioblastoma in order to develop novel clinical treatment modalities. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a member of the parvulin family; the peptidyl-prolyl cis/trans isomerase (PPIase) group of proteins (2). Previous data has identified that Pin1 is broadly overexpressed in various types of tumors, including gliomas (3). Members of the Parvulin family have a variety of functions, including modulating the assembly, folding, activation/inactivation and transport of essential proteins to their intracellular targets (4). In addition, the proteins regulate intracellular signaling, transcription, cell cycle progression and apoptosis by altering the function and/or stability of target proteins (5). Pin1 induces conformational changes in its target phospho-proteins by binding and isomerizing the peptidyl-prolyl bond in phosphorylated Ser/Thr-Pro motifs. Consequently, it has roles in a wide range of cellular activities, since Ser/Thr-Pro motifs are also specific phosphorylation sites on a number of protein kinases. Pin1 expression has been identified to be positively correlated with the expression of vascular endothelial growth factor (VEGF), a key molecule involved in angiogenesis. Pin1 is also known to indirectly regulate VEGF expression through the isomerization of the hypoxia-inducible factor 1 (HIF-1) and activating protein-1 (AP1) transcription factors (6). Furthermore, the overexpression of Pin1 in breast cancer cell lines has been demonstrated to lead to an upregulation in VEGF and a consequent promotion of angiogenesis during cancer progression (6). A previous study also revealed that Knockdown of Pin1 leads to reduced angiogenic potential and tumorigenicity in glioblastoma cells KUTAY DENIZ ATABAY1-3, MEHMET TAHA YILDIZ1,4*, TIMUCIN AVSAR1,2*, ARZU KARABAY2 and TÜRKER KILIÇ1,5 1Prof. Dr. Peter Black Laboratory of Molecular Neurosurgery, Institute of Neurological Sciences, Marmara University; 2Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Technical University; 4Department of Biology, Faculty of Arts and Science, Fatih University; 5Department of Neurosurgery, Faculty of Medicine, Bahcesehir University, Istanbul, Turkey Received June 30, 2014; Accepted March 30, 2015 DOI: 10.3892/ol.2015.3512 Correspondence to: Professor Türker Kiliç, Department of Neurosurgery, Faculty of Medicine, Bahcesehir University, Cıragan Caddesi, Osmanpasa Mektebi Sokak 4-6 Besiktas, Istanbul 34353,