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Role of Novel MicroRNAs in the PVT-1 Locus

$177,763Z01FY2008CANIH

Division Of Basic Sciences - Nci

Investigators

Abstract

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.

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