Evaluation of metastamiRs and interactions with rock kinases in Ewing's sarcomas: implications for tumor progression and invasion process

Abstract

The treatment of childhood cancer has evolved significantly in recent years, however, is mostly lagging behind. Ewing's sarcoma (EWS) is the second most common malignant bone tumor in the pediatric age, considered curable, though it presents great propensity for metastasis and relapses due to the inherent chemoresistance and invasiveness of cells. Recently, the metastamiRs and ROCK kinases have been identified as important contributors in the pathophysiology and progression of different tumors due to their role in cell migration. In fact, different studies suggest that blocking elements involved in the control of cell migration can reduce the opportunistic ability of tumor cells to invade and metastasize to distant organs, a step considered critical in targeted intervention. Thus, we propose to evaluate the expression of modulated metastamiRs associated with ROCK activity in samples of pediatric patients affected with EWS and to evaluate the in vitro effects of ectopic metastamiRs expression or inhibition in in EWS cell lines, emphasizing on the processes of proliferation, migration and invasion. Moreover, we also aim to assess the influence of ROCK inhibition on resistance and sensitization to treatments currently available. The metastamiRs that result in significant responses in vitro assays will be used to generate transformed cells for conducting future in vivo experiments in order to study the therapeutic potential of metastamiR relative tumor dissemination.