(Pro)renin receptor is crucial for glioma development via the Wnt/β-catenin signaling pathway
| Autor: | Keisuke Miyake, Takashi Tamiya, Masaaki Kouchi, Daisuke Ogawa, Yuki Shibayama, Akira Nishiyama |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Vacuolar Proton-Translocating ATPases Small interfering RNA Receptors Cell Surface Biology 03 medical and health sciences 0302 clinical medicine Cyclin D1 WNT2 Glioma Tumor Cells Cultured medicine Humans Receptor Wnt Signaling Pathway Brain Neoplasms Wnt signaling pathway General Medicine Middle Aged medicine.disease 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cancer research Female Signal transduction |
| Zdroj: | Journal of Neurosurgery. 127:819-828 |
| ISSN: | 1933-0693 0022-3085 |
| DOI: | 10.3171/2016.9.jns16431 |
| Popis: | OBJECTIVEThe (pro)renin receptor (PRR) plays an essential role in the early development of the central nervous system by activating the Wnt/β-catenin signaling pathway. The authors investigated the potential role of the PRR in the pathogenesis of glioma.METHODSThe authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 (IDH1R132H) in paraffin sections of 31 gliomas. Expression of the PRR and Wnt pathway components in cultured human glioma cell lines (U251MG, U87MG, and T98G) was measured using Western blotting. The effects of PRR short interfering RNA (siRNA) on glioma cell proliferation (WST-1 assay and direct cell counting) and apoptosis (flow cytometry and the caspase-3 assay) were also examined.RESULTSPRR expression was significantly higher in glioblastoma than in normal tissue or in lower grade glioma, regardless of IDH1R132H mutation. PRR expression was also higher in human glioblastoma cell lines than in human astrocytes. PRR expression showed a significant positive correlation with the Ki-67 labeling index, while it had a significant negative correlation with the survival time of glioma patients. Treatment with PRR siRNA significantly reduced expression of Wnt2, activated β-catenin, and cyclin D1 by human glioblastoma cell lines, and it reduced the proliferative capacity of these cell lines and induced apoptosis.CONCLUSIONSThis is the first evidence that the PRR has an important role in development of glioma by aberrant activation of the Wnt/β-catenin signaling pathway. This receptor may be both a prognostic marker and a therapeutic target for glioma. |
| Databáze: | OpenAIRE |
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