title: Tumor suppressor microRNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma.
abstract: The presence of tumor-specific microRNAs reflects tissue of origin and tumor stage. We show that the absence of miRNAs likewise can be used to determine tumor origin (miR-155) and proliferation state because tumor suppressor miRNAs (miR-222/221, let-7 family) were significantly down-regulated in primary effusion lymphoma (PEL) and in Kaposi sarcoma (KS), an endothelial cell tumor. PEL and KS are associated with KS-associated herpesvirus infection. We identified 15 virally regulated miRNAs in latently infected, nontumorigenic endothelial cells. MiR-143/145 were elevated only in KS tumors, not virally infected endothelial cells. Thus, they represent tumor-specific, rather than virus-specific, miRNAs. Because many tumor suppressor proteins are wild-type in KS and PEL, down-regulation of multiple tumor suppressor miRNAs provides a novel, alternative mechanism of transformation.
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research at University of North Carolina at Chapel Hill, NC 27599-7290, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: O'Hara
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Dezube
authors.forename: William J
authors.initials: WJ
authors.lastname: Harrington
authors.forename: Blossom
authors.initials: B
authors.lastname: Damania
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D054685:Lymphoma, Primary Effusion / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000235:genetics*
chemical_list: D035683:MicroRNAs