Tumor suppressor microRNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma.
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.
O'Hara
Andrea J
AJ
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.
Wang
Ling
L
Dezube
Bruce J
BJ
Harrington
William J
WJ
Damania
Blossom
B
Dittmer
Dirk P
DP
D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D054685:Lymphoma, Primary Effusion / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000235:genetics*
D035683:MicroRNAs