Role of Novel MicroRNAs in the PVT-1 Locus

对覆盖PVT1基因座的基因组序列进行了计算分析和实验验证，确定了7个miRNAs。几乎所有miRNA前体转录本在晚期B细胞(包括PCT和VBL细胞系)中的表达水平高于未成熟B细胞，提示可能在淋巴发育和/或淋巴瘤中发挥作用。此外，慢病毒载体介导的miR-15PVT1前体(人和鼠)在小鼠Pre-B细胞系中的过表达增加了Myc的表达，这表明靶点(S)的阶段特异性下调肯定对Myc的表达有一定的间接影响。在几个MYC/PVT1共扩增的上皮性癌细胞株中也发现了hsa-miR-15PVT1前体的高水平表达，这表明这些miRNAs在肿瘤发生中具有潜在的更广泛的作用。

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.