Pvt1-encoded microRNAs in oncogenesis.
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.


CONCLUSIONS
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.
Beck-Engeser
Gabriele B
GB
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA. Gabriele.Beck-Engeser@ucsf.edu
Lum
Amy M
AM
Huppi
Konrad
K
Caplen
Natasha J
NJ
Wang
Bruce B
BB
Wabl
Matthias
M
D000818:Animals; D015870:Gene Expression; D016259:Genes, myc; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000821:virology; D013950:Thymus Gland / Q000821:virology; D016662:Virus Integration / Q000235:genetics
D035683:MicroRNAs