title: MicroRNAs in rhabdomyosarcoma: pathogenetic implications and translational potentiality.
abstract: There is growing evidence that interconnections among molecular pathways governing tissue differentiation are nodal points for malignant transformation. In this scenario, microRNAs appear as crucial players. This class of non-coding small regulatory RNA molecules controls developmental programs by modulating gene expression through post-transcriptional silencing of target mRNAs. During myogenesis, muscle-specific and ubiquitously-expressed microRNAs tightly control muscle tissue differentiation. In recent years, microRNAs have emerged as prominent players in cancer as well. Rhabdomyosarcoma is a pediatric skeletal muscle-derived soft-tissue sarcoma that originates from myogenic precursors arrested at different stages of differentiation and that continue to proliferate indefinitely. MicroRNAs involved in muscle cell fate determination appear down-regulated in rhabdomyosarcoma primary tumors and cell lines compared to their normal counterparts. More importantly, they behave as tumor suppressors in this malignancy, as their re-expression is sufficient to restore the differentiation capability of tumor cells and to prevent tumor growth in vivo. In addition, up-regulation of pro-oncogenic microRNAs has also been recently detected in rhabdomyosarcoma.In this review, we provide an overview of current knowledge on microRNAs de-regulation in rhabdomyosarcoma. Additionally, we examine the potential of microRNAs as prognostic and diagnostic markers in this soft-tissue sarcoma, and discuss possible therapeutic applications and challenges of a "microRNA therapy".
authors.affiliation: Department of Oncohematology, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy. rossella.rota@opbg.net
authors.forename: Rossella
authors.initials: R
authors.lastname: Rota
authors.forename: Roberta
authors.initials: R
authors.lastname: Ciarapica
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy
chemical_list: D035683:MicroRNAs; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins