Role of Novel MicroRNAs in the PVT-1 Locus

对覆盖PVT1位点的基因组序列进行计算分析和实验验证，鉴定出7个mirna。与未成熟B细胞相比，几乎所有的miRNA前体转录物在晚期B细胞（包括PCT和vBL细胞系）中的表达水平都更高，这表明miRNA可能在淋巴细胞发育和/或淋巴瘤中发挥作用。此外，在小鼠b前细胞系中，慢病毒载体介导的miR-15PVT1前体（人和小鼠）的过表达增加了Myc的表达，这表明一个靶点的特异性下调一定对Myc的表达有一些间接影响。hsa-miR-15PVT1前体的高水平表达也出现在几种MYC/PVT1共扩增的上皮癌细胞系中，这表明这些mirna在肿瘤发生中可能具有更广泛的作用。

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.