miRNAs associated with breast cancer brain metastasis

The goal of this study is to determine the extracellular miRNAs associated with breast cancer metastasis to the brain. By combining the small RNA-seq data of patient sera and cell culture models, we are able to select breast cancer cell-derived miRNAs that are associated with brain metastasis for further functional study. We first performed small RNA-seq using serum RNA from 42 patients with stage IV breast cancer. These patients include 21 with brain metastases (cases) and 21 controls without brain metastases (but with metastases to other organs) that were selected to have matched age, time from diagnosis, and HER2/ER/PR status of the breast tumor. We next peformed small RNA-seq using RNA extracted from extracellular vesicles (EVs, including exosomes) and from cell lysate, to compare the extracellular and intracellular miRNA profiles between two isogenic cell lines, the parental MDA-MB-231 human breast cancer cell line and a brain-tropic variant of MDA-MB-231 that was selected in vivo for its enhanced potential to form brain metastasis.