MiR-296/Scribble axe is deregulated in human breast cancer and miR-296 restoration reduces tumor growth in vivo

MiR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation, and cancer. We hypothesized that miR-296-5p was involved in breast cancer onset and progression possibly through regulation of its target Scribble, a polarity protein recently implicated in the acquisition of cancer stem-cell traits and in cell motility. We found that miR-296-5p levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma and low expression of this miRNA predicted shorter disease-free survival independently of classic clinicopathological parameters. Further, reduced miR-296-5p levels were significantly correlated to earlier spread of cancer, in the overall series and in the subset with distant metastases. Opposite to its regulator, Scribble was overexpressed and mislocalized in primary breast cancers or locoregional or distant metastatic lesions compared to normal parenchyma. Notably, Scribble mislocalization was associated with breast cancer patients’ overall survival, metastatic spread and organ tropism. Finally, direct injection of a precursor miR-296-5p into tumors of a breast cancer xenograft model significantly decreased tumor growth. Our results show that the miR-296-5p/Scribble axe plays a role in breast carcinogenesis and miR-296-5p-based therapeutic approach hampers breast cancer tumor growth in vivo. Modulation of miR-296-5p may represent a new therapeutic option for breast cancer pati...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research