CBMT-01. PARAOXONASE-2 IS HIGHLY EXPRESSED IN GBM AND PROMOTES GBM CELL SURVIVAL
| Autor: | Edlira Hoxha, Hae-Ri Song, Hannah Cho |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Neuro-Oncology. 20:vi32-vi32 |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | Paraoxonase-2 (PON2), a member of paraoxonase family, is an anti-oxidant enzyme that is implicated in cell survival. Recent evidence demonstrated that PON2 promotes apoptosis resistance in the selective tumor cells. Here, we report genetic regulation and role of PON2 in glioma. We showed that PON2 is highly expressed in glioblastomas (GBM) compared to non-tumor brains and that high PON2 expression is associated with poor survival in patients with GBM. Functional studies showed that knockdown of PON2 inhibits cell growth, induces apoptosis, and increases pro-apoptotic factor CHOP. Using transcriptome and transcription factor motif analysis, we showed that Nuclear Factor I-A (NFIA), a glioma-promoting transcription factor, positively regulates PON2 transcription and protein level and that PON2 and NFIA expression is highly correlated in GBM. Moreover, NFIA directly regulated PON2 transcription through binding to the PON2 promoter. Consistent with this finding, PON2 knockdown-induced growth inhibition is reversed by ectopic expression of NFIA. Furthermore, Nfia-deficient brain shows decrease in expression of PON2, providing genetic evidence that supports NFIA-PON2 regulatory relationship. Collectively, these data suggest that the pro-survival effect of PON2 is at least partly mediated by NFIA in GBM, advancing our understanding of the emerging role of PON2 in glioma. |
| Databáze: | OpenAIRE |
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