ER homeostasis is regulated by multiple signaling pathways and is responsible for cell survival,28 angiogenesis29 and apoptosis.30 ER stress activates pathways that lead to unfolded protein response, which subsequently has a critical role in stimulating cell apoptosis.31, 32 Here, we found that both metformin and miR-708-5p can upregulate unfolded protein response proteins CHOP, p-eIF2α, CRT, GRP78 and ATP2A1, which indicates that metformin stimulates miR-708-5p to induce ER stress in prostate cancer cells. Here, ATP2A1 is linked to prostate cancer.