MicroRNAs 100 and 125b in Ewing sarcoma

Ewing sarcoma is a common cancer of bone and soft tissue affecting children and young adults. It is a very aggressive cancer with a poor long-term outcome. Even with the best chemotherapy, long-term survival for Ewing sarcoma patients is about 50%, drops to 25% for those presenting with metastatic disease, and plummets to 10% for patients with recurrent disease. Thus, there is a great need for new therapies for this disease. MicroRNAs (miRs) are recently discovered molecules normally occurring in cells, which have critical functions in normal physiology and in disease. Recent studies indicate that miRs play key roles in cancer, and identify miRs as important new anti-cancer agents and targets. However, very little is currently known about miRs in pediatric cancers and in sarcomas. Our laboratory is interested in understanding how miRs regulate the cancerous properties of Ewing sarcoma. Our ultimate goal is to identify new ways to target this aggressive disease. Using miR 'chip' technology, we have discovered a number of miRs which are expressed at very low levels in Ewing sarcoma cells, but highly expressed in cells made non-cancerous by turning off a critical cancer-causing protein, called EWS/Fli1. Our hypothesis is that such miRs limit the cancerous behavior of Ewing sarcoma. In early studies thus far, we have determined that two of the miRs do indeed exhibit such properties. In the proposed research, we wish to further understand how these miRs, individually and in combination, work to limit the cancerous potential of Ewing sarcoma and whether they could be used in addition to conventional chemotherapy for the treatment of this aggressive disease.