Prostate cancer (PCa) ranked the 5th most common cancer in the world. Recently, ROR2 had been reported to be a regulatory protein in noncanonical Wnt signaling. Wnt signaling played important role in regulation of PCa metastasis, we examined the role of ROR2 in PCa metastasis. Oncomine database and IHC revealed that both mRNA and protein level of ROR2 decreased in PCa tissues, while ROR2 mRNA level was the lowest in metastatic PCa. Moreover, PCa patients with lower mRNA level of ROR2 had poor survival rate and higher recurrent frequency. Over-expression of ROR2 in DU-145 and PC-3 PCa cells significantly suppressed cell migration, invasion and EMT markers. Micro-Western Array revealed that over-expression of ROR2 elevated protein expression of PIAS3, but decreased the abundance of Stat3, NF-&kappaB, and phosphorylation of Akt in PCa cells. Orthotopic xenograft mice model demonstrated that ROR2 can suppress PCa cells metastasis to lung. Over-expression of ROR2 suppressed expression level of miR199a-5p, and knockdown PIAS3 by over-expression of miR-199a-5p restored ROR2 mediated suppressive effect on PCa cell migration. Taken together, ROR2 is a novel tumor suppressor in PCa.
