The Role of Pseudogenes as Regulators of the IGF2BP2/IGF1R/RAS Axis in Rhabdomyosarcoma: Functional Characterization in Myogenesis and Implications for Anticancer Therapy

In the study of cellular mechanisms that are out of control in cancer, noncoding RNAs(ncRNAs) are becoming increasingly important: these are transcripts that do not code for proteins, but which frequently play regulatory roles by fine-tuning the function of other molecules with very relevant roles in the appearance and/or development of the tumor. Although the ncRNAs of the small type are generally very well characterized and their roles as pro- or anti-carcinogenic agents are well known, long ncRNAs, due to its great specificity and variety of action, are less understood. In our group, we have developed a series of techniques that have allowed us to identify one of these long ncRNAs, RPSAP52, which gives proliferative features to the cell and is characterized by being present in abundance during the development of the embryo and then disappearing in mature tissues. Also, we have data pointing to its essential role in the early stages of muscle development. Its recurrence is frequent in many different types of human tumors (including certain sarcomas and specially those of muscular origin, such as pediatric rhabdomyosarcoma). We have discovered that it exerts its mechanism of action by stimulating oncogenic pathways, so that if we artificially suppress its presence in cells in culture or in mice, we succeed in significantly reversing tumor growth. In the present project, we plan to delve into the mechanism of action of RPSAP52 in cell tumor models as well as in normal myogenesis, to understand in depth its regulatory role on the expression and action of other oncogenes. In addition, we will perform an unbiased screen to reveal other long ncRNAs with oncogenic features similar to RPSAP52in the context of rhabdomyosarcoma. Due to their easy handling and lack of function in normal tissues, these molecules can be a new therapeutic tool of great interest in the clinics.