Research
Pvt1-encoded microRNAs in oncogenesis
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* Corresponding author: Matthias Wabl mutator@ucsf.edu
- † Equal contributors
1 Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA
2 Picobella, L.L.C., 863 Mitten Road, Suite 101, Burlingame, CA 94010, USA
3 Gene Silencing Section, Genetics Branch, Center Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
Retrovirology 2008, 5:4 doi:10.1186/1742-4690-5-4
Published: 14 January 2008Abstract
Background
The functional significance of the Pvt1 locus in the oncogenesis of Burkitt's lymphoma and plasmacytomas has remained a puzzle. In these tumors, Pvt1 is the site of reciprocal translocations to immunoglobulin loci. Although the locus encodes a number of alternative transcripts, no protein or regulatory RNA products were found. The recent identification of non-coding microRNAs encoded within the PVT1 region has suggested a regulatory role for this locus.
Results
The mouse Pvt1 locus encodes several microRNAs. In mouse T cell lymphomas induced by retroviral insertions into the locus, the Pvt1 transcripts, and at least one of their microRNA products, mmu-miR-1204 are overexpressed. Whereas up to seven co-mutations can be found in a single tumor, in over 2,000 tumors none had insertions into both the Myc and Pvt1 loci.
Conclusion
Judging from the large number of integrations into the Pvt1 locus – more than in the nearby Myc locus – Pvt1 and the microRNAs encoded by it are as important as Myc in T lymphomagenesis, and, presumably, in T cell activation. An analysis of the co-mutations in the lymphomas likely place Pvt1 and Myc into the same pathway.