miR-296/Scribble axis is deregulated in human breast cancer and miR-296 restoration reduces tumour growth in vivo
| Autor: | Paolo Foa, Federica Savi, S. Caldiera, Silvano Bosari, Valentina Vaira, Dario Ricca, Andrea Luciani, Stefano Gatti, Irene Forno, Alice Faversani, Gaetano Bulfamante |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
SCRIB Oncology CA15-3 medicine.medical_specialty Cellular differentiation Breast Neoplasms Biology Breast cancer Cell Movement Cancer stem cell Cell Line Tumor Internal medicine microRNA medicine Humans Aged Cell Proliferation Aged 80 and over Tumor Suppressor Proteins Membrane Proteins Cancer Cell Differentiation General Medicine Middle Aged medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Female Breast carcinoma Signal Transduction |
| Zdroj: | Clinical Science. 127:233-242 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20130580 |
| Popis: | miR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation and cancer. We hypothesized that miR-296-5p is involved in breast cancer onset and progression possibly through regulation of its target SCRIB (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 with an earlier spread of cancer in the overall series and with distant metastases in the subset. In contrast with its regulator, SCRIB was overexpressed and mislocalized in primary breast cancers or locoregional or distant metastatic lesions compared with normal parenchyma. Notably, SCRIB mislocalization was associated with overall survival, metastatic spread and organ tropism in patients with breast cancer. Finally, direct injection of a precursor miR-296-5p into tumours of a breast cancer xenograft model significantly decreased tumour growth. Our results show that the miR-296-5p/SCRIB axis plays a role in breast carcinogenesis and an miR-296-5p-based therapeutic approach hampers breast cancer tumour growth in vivo. Modulation of miR-296-5p may represent a new therapeutic option for patients with breast cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|