Submitted September 16, 2008
Accepted December 24, 2008
Tumor suppressor micro RNAs are underrepresented in primary effusion lymphoma and Kaposi sarcoma
Andrea J. O'Hara, Ling Wang, Bruce J. Dezube, William J. Harrington Jr., Blossom Damania, and Dirk P. Dittmer*
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research at the University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States
The Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United States
* Corresponding author; email: ddittmer{at}med.unc.edu.
The presence of tumor specific microRNAs reflects tissue of origin and tumor stage. (a) We show that the absence of miRNAs likewise can be used to determine tumor origin (miR-155) and proliferation state, since tumor suppressor miRNAs (miR-222/221, let-7 family) were significantly downregulated in primary effusion lymphoma (PEL) and in Kaposi sarcoma (KS), an endothelial cell tumor. PEL and KS are associated with Kaposi sarcoma-associated herpesvirus infection. (b) We identified fifteen virally-regulated miRNAs in latently infected, non-tumorigenic endothelial cells (EC). (c) MiR-143/145 were elevated only in KS tumors, not virally-infected EC. Thus they represent tumor-specific, rather than virus-specific miRNAs. Since many tumor suppressor proteins are wild-type in KS and PEL, downregulation of multiple tumor suppressor miRNAs, provides a novel, alternative mechanism of transformation.
