Institute of Cellular and Molecular Medicine, DNA Tumor Virus Laboratory, University of Copenhagen, Panum Institute, Blegdamsvej 3, 2200 Copenhagen, Denmark.
Biochem Biophys Res Commun. 2011 Aug 19;412(1):20-5. doi: 10.1016/j.bbrc.2011.07.011. Epub 2011 Jul 18.
Human papillomaviruses (HPVs) are highly prevalent giving rise to both benign and malignant lesions why they are classified as high- and low-risk viruses. In this study we selected one low-risk (HPV 11) and two high-risk (HPV 16 and -45) types for genomewide miRNA analysis to investigate possible common and distinct features in the expression profiles. For this purpose we developed a cell culture model system in HaCaT cells for expression of the viral genomes under standardized conditions. We identified 25 miRNAs which were differentially regulated in two or three HPV types where 13 miRNAs were in common for all three types. Among the miRNAs identified, miR-125a-5p, miR-129-3p, miR-363, and miR-145 are related to human cancers. Noteworthy, miR-145 is found upregulated in the miRNA profiles of both high-risk HPV types. For selected differentially expressed miRNAs in HPV 16 predicted miRNA target transcript involved in signal transduction, RNA splicing and tumor invasive growth were validated by qRT-PCR. In addition, our results imply that the early 3' untranslated region (3'UTR) of the three HPV genomes were not a target for miRNA regulation.
人乳头瘤病毒（HPV）高度流行，导致良性和恶性病变，因此它们被分类为高风险和低风险病毒。在这项研究中，我们选择了一种低风险（HPV 11）和两种高风险（HPV 16 和 -45）类型进行全基因组 miRNA 分析，以研究表达谱中可能存在的共同和独特特征。为此，我们在 HaCaT 细胞中开发了一种细胞培养模型系统，用于在标准化条件下表达病毒基因组。我们确定了 25 个在两种或三种 HPV 类型中差异表达的 miRNA，其中 13 个 miRNA 是所有三种类型共有的。在鉴定出的 miRNA 中，miR-125a-5p、miR-129-3p、miR-363 和 miR-145 与人类癌症有关。值得注意的是，miR-145 在两种高危 HPV 类型的 miRNA 谱中均上调。对于 HPV 16 中差异表达的选定 miRNA，通过 qRT-PCR 验证了参与信号转导、RNA 剪接和肿瘤侵袭性生长的预测 miRNA 靶转录物。此外，我们的结果表明，三种 HPV 基因组的早期 3'非翻译区（3'UTR）不是 miRNA 调节的靶标。
