Abstract

Abstract Recent studies have suggested a significant role of microRNAs (miRNAs) in the regulation of cancer development. This study examined whether they play a role in breast cancer progression.A miRNA microarray analysis was performed on laser-capture microdissected breast tumors of different lymph-node metastasis status showing different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify specific miRNAs that exhibit significant differences in expression. Functional interaction between the candidate miRNA (i.e. miR-30a) and the gene (i.e. Vim gene, coding for vimentin, a protein involved in epithelial-mesenchymal transition) possibly regulated by miR-30a was verified. We further examined whether decreased expression of miR-30a was associated with breast cancer progression.miR-30a negatively regulated vimentin expression, by binding to the 3′-untranslated region of Vim. Ectopic expression of miR-30a was found to suppress the migration and invasiveness phenotypes of breast cancer cell lines. More importantly, breast cancer patients with decreased miR-30a level in primary cancerous sites were found to be associated with poor clinical features (late tumor stage and lymph node metastasis) and worse progression, demonstrating an increased hazard ratio (HR) for recurrence or recurrence plus mortality during the follow-up period (P<0.05). These findings provide a support of clinical importance of miR-30a in mediating breast tumor progression. Identification of miR-30a-mediated regulation of vimentin might provide a promising therapeutic target in treating breast cancer. 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 1094. doi:1538-7445.AM2012-1094

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