In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 145-145
Abstract:
Background Glioblastoma is the most common malignant primary brain tumor in adults. While increasing evidence indicates that the deregulation of miRNAs is involved in a wide range of human cancers, the roles and potential mechanisms of miRNA in glioma development and progression are still largely unknown. Methods The expression of miR-23b in 48 clinical samples and five glioma cell lines with different grades was examined by FISH and qRT-PCR. Flow cytometry, Annexin V method, Colony formation assay, and Transwell cell invasion test were used to detect the proliferation and invasive activity of the tumor cells before and after transfection with AS-miR-23b of glioma cells. Luciferase assay and western blot analysis were used to examine that VHL is a direct target of miR-23b. In vivo anti-glioma effect of AS-miR-23b was investigated using subcutaneous xenograft models. Results We identified that expression of miR-23b is elevated in both glioma tissue samples and glioma cells by real-time PCR and FISH analyses. Knock-down of miR-23b expression triggered growth inhibition, induced apoptosis and suppressed invasion of glioma cells in vitro. Luciferase assay and western blot analysis revealed that VHL is a direct target of miR-23b. As such, restored expression of VHL inhibited glioma cell survival and induced apoptosis. Mechanistic investigation revealed that miR-23b deletion decreased HIF-1α/VEGF expression and suppressed β-catenin/Tcf-4 transcription activity in a VHL-dependent manner. Furthermore, expression of VHL was inversely correlated with miR-23b in glioblastoma samples and was predictive of patient survival in a retrospective analysis. Conclusion In summary, we demonstrate that down-regulation of miR-23b inhibits survival and invasion of glioma by repressing expression of VHL. Genetic restoration of VHL bypassed the effects of miR-23b overexpression, suppressing the ranscriptional activities of both the HIF/VEGF and β-catenin/Tcf-4 pathways. Based upon these observations, we propose that anti-angiogenic therapy for glioma could benefit from adjuvent miRNA therapy targeting the HIF1α and β-catenin/Tcf-4 pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 145. doi:1538-7445.AM2012-145
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-145
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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