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首页> 外文学位 >Characterization of cellular and viral microRNAs in Kaposi's sarcoma-associated herpesvirus malignancies.
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Characterization of cellular and viral microRNAs in Kaposi's sarcoma-associated herpesvirus malignancies.

机译：卡波西氏肉瘤相关疱疹病毒恶性肿瘤中细胞和病毒microRNA的表征。

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摘要

MicroRNAs (miRNAs) are a class of small non-coding functional RNAs that mediate post-transcriptional regulation of target mRNAs in a sequence-specific manner. They affect a wide variety of cellular processes, ranging from cellular differentiation, proliferation, apoptosis, metabolism, infection and cancer. MicroRNAs are regulated by gene copy number alteration, transcription, and processing. Over the past few years, miRNAs have also been shown to be encoded in a number of viruses, including herpesviruses. The viral-encoded miRNAs are important regulators in both the viral life cycle and virus-host interaction, specifically viral oncogenesis. Kaposi's Sarcoma-associated Herpesvirus encodes 12 viral miRNA genes. It is the causative agent of primary effusion lymphoma (PEL), a non-Hodgkin lymphoma (NHL) of B cell lineage, and Kaposi's sarcoma (KS), a highly vascular AIDS-defining cancer of endothelial cell lineage.;Using real-time quantitative polymerase chain reaction (QPCR)-based arrays, changes were determined in miRNA gene copy number, pre-miRNA, and mature cellular miRNA levels for the largest set of PEL examined to date. This defined the miRNA signature of PEL, which differs from that of other NHL. Furthermore it showed that transcriptional regulation of pre-miRNA as well as mature miRNA levels contribute nonredundant information that can be used for the classification of human tumors. Not only the induction, but also the absence of specific cellular miRNAs can be used to determine tumor origin and proliferation state. Tumor suppressor miRNAs were significantly down regulated in PEL as well as in KS. These represent tumor-specific, rather than virus-specific miRNAs. Since many known tumor suppressor proteins are wild type in KS and PEL, down regulation of multiple tumor suppressor miRNAs, provides a novel, alternative mechanism of transformation. Finally, using precursor microRNA profiling by a novel real-time QPCR method progressive stages of endothelial cell transformation cumulating in KS was defined; and particular miRNAs that serve as biomarkers for tumor progression were identified. For the first time, comprehensive comparisons were possible between primary patient biopsies, well-established culture and mouse tumor models. All together, these results can be used to characterize the cellular miRNA signature in KSHV-associated malignancies, namely PEL and KS.
机译：微小RNA（miRNA）是一类小的非编码功能性RNA，以序列特异性方式介导目标mRNA的转录后调控。它们影响多种细胞过程，包括细胞分化，增殖，凋亡，代谢，感染和癌症。 MicroRNA受基因拷贝数改变，转录和加工调控。在过去的几年中，miRNA还显示出在多种病毒（包括疱疹病毒）中编码。病毒编码的miRNA在病毒生命周期和病毒-宿主相互作用（尤其是病毒致癌作用）中都是重要的调控因子。卡波济氏肉瘤相关疱疹病毒编码12种病毒miRNA基因。它是原发性渗出性淋巴瘤（PEL），B细胞谱系的非霍奇金淋巴瘤（NHL）和卡波西肉瘤（KS）的病原体，Kaposi肉瘤是一种高度血管性的AIDS定义的内皮细胞谱系。基于定量聚合酶链反应（QPCR）的阵列，确定了迄今检查的最大的PEL组的miRNA基因拷贝数，pre-miRNA和成熟细胞miRNA水平的变化。这定义了PEL的miRNA签名，与其他NHL的miRNA签名不同。此外，它表明pre-miRNA的转录调控以及成熟的miRNA水平贡献了可用于人类肿瘤分类的非冗余信息。不仅诱导，而且不存在特异性细胞miRNA，都可以用于确定肿瘤起源和增殖状态。 PEL和KS中的肿瘤抑制miRNA均显着下调。这些代表肿瘤特异性而非病毒特异性miRNA。由于许多已知的肿瘤抑制蛋白在KS和PEL中是野生型，因此多种肿瘤抑制miRNA的下调可提供一种新颖的替代转化机制。最后，使用通过新型实时QPCR方法进行的前体microRNA分析，确定了累积在KS中的内皮细胞转化的进行阶段；并鉴定了可作为肿瘤进展生物标志物的特定miRNA。首次，首次患者活检，完善的培养和小鼠肿瘤模型之间的全面比较成为可能。总之，这些结果可用于表征与KSHV相关的恶性肿瘤，即PEL和KS中的细胞miRNA特征。

著录项

  • 作者

    O'Hara, Andrea J.;

  • 作者单位

    The University of North Carolina at Chapel Hill.;

  • 授予单位 The University of North Carolina at Chapel Hill.;
  • 学科 Biology Genetics.;Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 195 p.
  • 总页数 195
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遗传学;微生物学;
  • 关键词

  • 入库时间 2022-08-17 11:38:28

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