Upregulation of microRNAs to redirect fusion-negative rhabdomyosarcoma towards a myogenic phenotype

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population, and fusion-negative RMS (FN-RMS) is the most common subtype. Current murine models fail to recapitulate the features observed in patients. At the same time, currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of RMS. In this PhD tenure work, we first developed a novel genetically engineered murine model of FN-RMS. This model showed metastatic capabilities and thus can be used to develop more effective treatments in high-risk FN-RMS patients. Both at the histologic and molecular level, the tumors developing in the murine model were shown to be similar to the ones observed in patients. Subsequently, we performed RNAseq on the cell lines obtained from the murine model of FN-RMS and addressed the use of a previously identified promyogenic microRNA cocktail in restoring the myogenic propensity of FN-RMS. Finally, we aimed at assessing the effects of oncosuppressor miRNAs in RMS by identifying a selection of miRNAs poorly present in samples from patients diagnosed with RMS. Together, our data established a novel model for FN-RMS that can be used to investigate the development of the tumor in high risk patients, and we were able to address the use of promyogenic miRNAs or oncosuppressor miRNAs in the tumor.

Publication year:2021

Accessibility:Open