miR-181b/Oncostatin m axis inhibits prostate cancer bone metastasis via modulating osteoclast differentiation

The activation of osteoblasts is significantly correlated to prostate tumor bone metastasis and bone loss. Oncostatin M (OSM) could promote breast cancer metastasis to bone. However, its role and mechanism in prostate cancer bone metastasis remain unclear. MicroRNAs (miRNAs) could play important roles in cancers via post-transcriptionally regulating target genes via binding to specific sequences in the 3' UTR of downstream target genes. In the present study, we performed microarray profiling analyses to identify differentially-expressed miRNAs in preosteoclast before and after osteoclast differentiation that could target OSM. miR-181b-5p was downregulated during Raw264.7 cells differentiation into osteoclast. By direct targeting OSM 3' UTR, miR-181b-5p inhibited OSM messenger RNA expression and protein levels, subsequently decreasing IL-6 and AREG and increasing OPG, while OSM overexpression exerted an opposing effect. More importantly, co-culture with miR-181b-5p-overexpressing differentiated Raw264.7 cells suppressed proliferation, migration, and invasion of mouse prostate cancer RM-1 cells, while co-culture with OSM-overexpressing Raw264.7 cells led to opposing cellular effects. More importantly, the effects of miR-181b-5p on osteoclastogenic factors and RM-1 cells could be significantly reversed by OSM overexpression. In summary, miR-181b-5p/OSM axis could be a viable therapeutic target for patients with surgically removed primary tumors to reduce bone metastasis and prevent bone loss.