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  • Author or Editor: Akira Ogawa x
  • By Author: Nishiyama, Akira x
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Masaaki Kouchi, Yuki Shibayama, Daisuke Ogawa, Keisuke Miyake, Akira Nishiyama and Takashi Tamiya

OBJECTIVE

The (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.

METHODS

The authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 (IDH1 R132H) 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.

RESULTS

PRR expression was significantly higher in glioblastoma than in normal tissue or in lower grade glioma, regardless of IDH1 R132H 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.

CONCLUSIONS

This 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.

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Vladislav Pavlov, Pascale Varlet, Fabrice Chretien, Geneviève Nguyen and Johan Pallud