Prostate Cancer-Secreted Exosomal miR-1275 Modulates Osteoblast Proliferation and Differentiation by Targeting SIRT2/RUNX2 Cascade

Abstract

BackgroundCancer-derived exosomes can promote tumor metastasis by delivering miRNAs from cancer cells to recipient cells. miR-1275 is suggested to be an important regulator involved in prostate cancer (PCa) metastasis; however, the association of miR-1275 with the microenvironment of PCa bone metastasis is unclear.Materials and methodsThe level of relative genes and proteins were detected by qPCR and western-blot, cell ability were examined by CCK-8 , the identification of target gene was analyzed by dual-luciferase reporter assay,exosomes were isolated from the PC3-derived conditioned medium by ultracentrifugation.Resultwe found that miR-1275 could be transferred from PCa cells to osteoblasts via exosomes. Exosomal miR-1275 significantly accelerated the proliferation of osteoblasts and the expression levels of osteoblast-specific genes, such as osteocalcin (OCN), type I collagen (COL-1), and osteopontin (OPN). Moreover, exosomal miR-1275 increased the expression of RUNX2, a master modulator of osteoblast differentiation, by down-regulation of SIRT2, which in turn influenced the proliferation and differentiation of osteoblasts.ConclusionsOur findings indicate that exosomal miR-1275 is a promoter of osteoblast activity, which may contribute to PCa bone metastasis.