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Molecular and Cellular Biology

Abstract 1960: Implication of miR-34a in radioresistance of bladder cancer .

Jose J. Mansure, Roland Nassim and Wassim Kassouf
Jose J. Mansure
McGill Urologic Oncology Research, Montréal, Quebec, Canada.
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Roland Nassim
McGill Urologic Oncology Research, Montréal, Quebec, Canada.
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Wassim Kassouf
McGill Urologic Oncology Research, Montréal, Quebec, Canada.
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DOI: 10.1158/1538-7445.AM2013-1960 Published April 2013
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Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Abstract

Purpose : Investigate resistance of radiation via miR-34a expression in human urothelial carcinoma

Methods : Human urothelial carcinoma cell lines derived from well-differentiated superficial bladder tumors as well as from high-grade invasive tumors were screened for their sensitivity to radiation. Growth inhibition was monitored by clonogenic assays. qRT-PCR analysis was used to evaluate expression of miR-34a among the human urothelial carcinoma cell lines. Methylation-specific polymerase chain reaction (MSP) was performed to determine CpG methylation status of miR-34a gene promoter among the cell lines. Association between miR-34a and sensitivity to radiation was also investigated by ectopic expression of miR-34a. Western blot was performed to evaluate protein expression.

Results: Remarkable differences in sensitivity to radiation have been shown among those cell lines in vitro. Of interest, miR-34a expression correlates with human bladder cancer cell response to radiation, with resistant cell lines showing lower expression of miR-34a and that is due to CpG methylation of its promoter. Additionally, an inverse correlation was observed between miR-34a and expression of sirtuin1 (SIRT1). Ectopic expression of miR-34a in cell lines resistant to radiation showed a positive effect of miR-34a to the response therapy. Growth inhibition observed after treatment could be explained, in part, by the increased expression of the cell cycle inhibitor p21.

Conclusion: Preliminary results suggest that detection of miR-34a expression may potentially be used as a predictor of therapeutic efficacy, and its regulation represent an attractive mechanism for the management of bladder cancer therapy.

Citation Format: Jose J. Mansure, Roland Nassim, Wassim Kassouf. Implication of miR-34a in radioresistance of bladder cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2013-1960

  • ©2013 American Association for Cancer Research
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Cancer Research: 73 (8 Supplement)
April 2013
Volume 73, Issue 8 Supplement
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Abstract 1960: Implication of miR-34a in radioresistance of bladder cancer .
Jose J. Mansure, Roland Nassim and Wassim Kassouf
Cancer Res April 15 2013 (73) (8 Supplement) 1960; DOI: 10.1158/1538-7445.AM2013-1960

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Abstract 1960: Implication of miR-34a in radioresistance of bladder cancer .
Jose J. Mansure, Roland Nassim and Wassim Kassouf
Cancer Res April 15 2013 (73) (8 Supplement) 1960; DOI: 10.1158/1538-7445.AM2013-1960
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
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