Breast cancer is the most frequently diagnosed cancer in women and the second leading cause of female cancer related death. Despite significant advances in early detection, surgery and therapy, treatment remains a challenge if metastatic disease develops. Metastasis occurs with high frequency in triple negative (ER/PR/HER2 negative, TNBC) breast cancers, which are a heterogeneous group of cancers with poor clinical outcome. We used an integrated approach to identify miRNAs that influence breast cancer metastasis as well as indicate patient outcome. Through this we identified miR-342 which we found is: (1) strongly downregulated in mouse and human TNBC cell lines that are prone to metastasise, (2) sufficient to repress breast cancer metastasis in immune competent and xenograft mouse models, and (3) an independent prognostic marker of patient outcome in large patient cohorts. Using genome-wide Argonaute-CLIP analysis we identified 120 direct target genes of miR-342, including a high representation of E2F1-driven and actin dynamics pathways. We propose these pathways may represent new targets for treatment of metastatic TNBC.
17 Mar 2019 - 20 Mar 2019