Taken together, our studies demonstrate that: 1) miR-21 up-regulated HIF-1α and VEGF expression and induced angiogenesis in prostate cancer cells; 2) miR-21 induced HIF-1α and VEGF expression through targeting PTEN, thus regulating AKT and ERK pathways; 3) both PI3K/AKT and ERK pathways are required for miR-21-inducing angiogenesis; 4) HIF-1α is an essential downstream effecter of miR-21 in mediating angiogenesis, and HIF-1α is regulated by miR-21 through the activation of AKT and ERK in the cells. Here, PTEN is linked to prostate cancer.