Abstract 3084: miR509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF alpha.

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Abstract Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the rate of one year survival among these patients remains less than 20%. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of breast tumor metastasis to the brain is poorly understood. Recent active research in microRNA identified a series of this type of molecules that are involved in tumor progression in various tumors as oncogenes and tumor suppressors. In this study, we have isolated RNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling. The results of our profile analysis for these samples revealed that primary tumor samples expressed significantly high level of miR509 compared to brain metastatic lesions. We also found that this microRNA was capable of modulating two essential genes for invasion, RhoC and TNF alpha. Interestingly, high expression of TNF alpha was significantly and inversely correlated to brain metastasis-free survival of breast cancer patients. Importantly, we found that the expression of miR509 significantly suppressed the ability of cancer cells to metastasize to the brain in our animal model. We also examined the expression of TNF alpha in brain-metastatic lesions and found that it was indeed significantly up-regulated. Furthermore, the results of our in vitro experiments indicate that miR509 attenuates the abilities of invasion of breast cancer cells by modulating the RhoC expression. These results suggest that miR509 may serve as a biomarker or therapeutic targets for brain metastasis of breast cancer. Citation Format: Fei Xing, Hiroshi Okuda, Aya Kobayashi, Puspa R. Pandey, Sambad Sharma, Yin-Yuan Mo, Yin Liu, Kerui Wu, Kounosuke Watabe. miR509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF alpha. [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 3084. doi:10.1158/1538-7445.AM2013-3084 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.