Ljepoja B, et al. - Since microRNA-27a (miR-27a), a small non-coding RNA has been reported to have a role in the regulation of Estrogen-Receptor α (ERα) expression in breast cancer and most ERα positive tumors are treated with Selective Estrogen Receptor Modulators (SERMs), researchers investigated the role of miR-27a expression in response to SERM treatment in breast cancer. They generated tamoxifen resistant cells by molecular evolution with six cycles of tamoxifen treatment. They either treated MCF7 and T47D luminal A breast cancer cell lines with miR-27a mimics, or ectopically modulated ER-signaling. They used RT-qPCR, western blotting and transcriptional activity ERE-reporter assays to assess the changes. Using cell viability and apoptosis measurements, they determined response to SERM treatments (tamoxifen, endoxifen and toremifen). Decreased expression of ERα and miR-27a was seen on tamoxifen-resistant cells. ERα levels increased with the overexpression of miR-27a, while modulation of ERα decreased miR-27a expression. Overall, based on a positive feedback loop with ERα, the sensitization of luminal A breast cancer cells to SERM treatments was induced by miR-27a. ER-positive breast cancer patients that received endocrine treatments and demonstrated high miR-27a levels had increased overall-survival.