title: Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma in the pediatric population. As this tumor has an undifferentiated myogenic phenotype, agents that promote differentiation hold particular promise as part of a novel therapeutic approach to combat this type of cancer. In this report, we focus on the contribution of two microRNAs (miRNAs) in rhabdomyosarcomas. Levels of miR-1 and miR-133a are drastically reduced in representative cell lines from each major rhabdomyosarcoma subtype (embryonal and alveolar). Introduction of miR-1 and miR-133a into an embryonal rhabdomyosarcoma-derived cell line is cytostatic, thereby suggesting a tumor suppressor-like role for these myogenic miRNAs. Transcriptional profiling of cells after miR-1 and miR-133a expression reveals that miR-1 (but not miR-133a) exerts a strong promyogenic influence on these poorly differentiated tumor cells. We identify mRNAs that are down-regulated by these miRNAs and propose roles for miR-1 and miR-133a in repressing isoforms of genes that are normally not expressed in muscle. Finally, we show that mRNA targets of miR-1 and miR-133a are up-regulated in rhabdomyosarcomas, suggesting a causative role for these miRNAs in the development of rhabdomyosarcomas. More important, these results point to the promise of enhancing rhabdomyosarcoma therapy using miRNAs as agents that mediate cytostasis and promote muscle differentiation.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Rao
authors.forename: Edoardo
authors.initials: E
authors.lastname: Missiaglia
authors.forename: Lauren
authors.initials: L
authors.lastname: Shields
authors.forename: Greg
authors.initials: G
authors.lastname: Hyde
authors.forename: Bingbing
authors.initials: B
authors.lastname: Yuan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Shepherd
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology*
chemical_list: D035683:MicroRNAs
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