Role of Novel MicroRNAs in the PVT-1 Locus

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Computational analysis of the genomic sequence covering the PVT1 locus and experimental verification identified seven miRNAs. Virtually all the miRNA precursor transcripts are expressed at higher levels in late-stage B cells (including PCT and vBL cell lines) compared to immature B cells suggesting possible roles in lymphoid development and/or lymphoma. In addition, Lentiviral vector-mediated overexpression of the miR-15PVT1 precursor (human and mouse) in a mouse pre-B cell line increased expression of Myc, suggesting that a stage specific down-regulation of a target(s) must have some indirect effect on Myc expression. High levels of expression of the hsa-miR-15PVT1 precursor is also seen in several epithelial cancer cell lines with MYC/PVT1 co-amplification suggesting a potentially broader role for these miRNAs in tumorigenesis.