P19. Inhibition Of Microrna 126 Leads To Complete Regression Of Hemangioendothelioma Tumors In Mice

Abstract

PURPOSE: We have previously shown that urinary microRNA126 (miR126) levels are a biomarker for hemangioma growth based on a prospective longitudinal study of children with hemangiomas and healthy age matched controls. We sought to determine the significance of miR126 on the regulation of hemangioma growth using a validated mouse model. METHODS: qPCR measurement of miR126 levels was done in EOMA cells and non-tumor forming endothelial cells. 6 weeks old female 129P/3 mice received a subcutaneous injection of 5x106 EOMA cells. 4 days post injection tumors were visible and topical administration of control antagomiR (n=8) or miR126 antagomiR (n=15) delivered transcutaneously using tissue nanotransfection electroporation technique. Treatments were given twice weekly. RESULTS: EOMA cells had 8,000-fold increase in miR126 levels compared to non-tumor forming endothelial cells. Control mice had significantly larger tumors with 100% mortality by 17 days post EOMA cell injection. miR126 antagomiR treated mice were significantly different from controls with decreased mortality (40%), smaller tumor size, prolonged survival with the last mouse death at 29 days post-injection, complete tumor regression by 6 weeks (n=9) and no observed recurrence at 90 days. CONCLUSION: These are the first results to demonstrate complete regression of hemangioendothelioma in response to miR26 inhibition. Elevation of miR126 levels in human hemangioma and murine hemangioendothelioma indicate shared mechanisms of growth. These findings demonstrate that miR126 is necessary for growth of both tumor types and represents a valid therapeutic target to treat hemangiomas.