Abstract
When brain metastasis develops, the prognosis of cancer is dismal. Insights into the biology of the primary cancer and the brain metastasis are necessary to inform more effective and targeted treatments. To study the role of microRNAs in brain metastasis, we performed differential expression profiling of 12 primary tumors and their paired brain metastases using smRNAseq (the 12 primary tumors included three non-small cell carcinomas, three melanomas, three endometrial carcinomas, one breast carcinoma, one thyroid carcinoma and one renal-cell carcinoma). To start, we identified microRNAs that were either highly upregulated or downregulated in the brain metastasis samples as compared to the paired primary tumors. After confirmation with real-time quantitative PCR, we further investigated the top microRNAs from both groups through functional assays performed in cell lines generated from primary melanoma, melanoma lymph node metastasis, and melanoma brain metastasis. From this top-down, patient sample to model cell-line approach we identified two microRNAs that are potentially important regulators in the development of brain metastasis. Characterization of their targets and their interactions may offer a therapeutic opportunity to improve the prognosis of patients with brain metastasis.