RPMS1 circular RNAs in EBV malignancies

EBV 恶性肿瘤中的 RPMS1 环状 RNA

基本信息

批准号：
10153734
负责人：
ERIK K FLEMINGTON
金额：
$ 36.6万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10153734
关键词：
AIDS-Related Lymphoma Address Animal Model Apoptosis Automobile Driving Biology Cancer Etiology Cancer Patient Carcinoma Cell Cycle Progression Cell Death Cell Line Cell Proliferation Cells Cellular Stress Characteristics Chromatin Communities DNA Polymerase II Data Detection Development Disease EBV-associated disease Environment Epstein Barr Virus associated tumor Epstein-Barr Virus Infections Epstein-Barr Virus latency Etiology Gene Expression Gene Expression Regulation Genes Genetic Transcription Goals Growth HIV Health Herpesviridae Hodgkin Disease Human Human Herpesvirus 4 Human Herpesvirus 8 Immune Immunologic Surveillance In Vitro Incidence Infection Introns Investigation Lead Link Lymphocryptovirus Lymphoma Lytic Maintenance Malignant Neoplasms Mediating MicroRNAs Molds Muridae Nasopharynx Carcinoma Non-Hodgkin&apos s Lymphoma Oncogenic Oncogenic Viruses Overlapping Genes Pathway interactions Patients Penetrance Phase Phenotype Play Poly A Porifera Process Protein Isoforms Proteins RNA RNA Splicing Regulation Research Rhesus Role S Phase Sampling Signal Transduction Specimen Time Transcript Untranslated RNA Viral Viral Genes Viral Proteins Virus Virus Diseases Virus Latency Virus Replication Work adaptive immune response cancer cell cell growth cell growth regulation cell type circular RNA gammaherpesvirus immune clearance in vivo latent gene expression malignant stomach neoplasm new therapeutic target prevent programs promoter response therapeutic candidate therapeutic target transcriptome tumor tumor growth tumorigenesis virus related cancer

项目摘要

Summary EBV is a human tumor virus that is an etiological agent in Hodgkin's lymphoma, non-Hodgkin's lymphomas, stomach cancer and nasopharygeal carcinoma, and it is associated with an increased incidence of lymphomas in the HIV-infected patient context. EBV contributes to oncogenic progression through the expression of one or more viral genes that activate oncogenic pathways along the progression of stages that lead to cancer. A unique aspect of herpesviruses is their utilization of “latency” gene expression programs where no virus replication occurs and only a small subset of viral genes is expressed that remodels the host cell environment to facilitate viral maintenance and persistence. With some of the pathways altered by latency genes overlapping with pathway alterations required for oncogenesis, EBV latency genes are key contributors to the tumor phenotype. Because non-coding RNAs do not elicit adaptive immune responses, the utilization of viral non-coding RNAs in latency settings is a key herpesviral strategy to sustain viral persistence in vivo without promoting immune clearance. We have discovered that EBV expresses a class of largely non-coding RNAs referred to as circular RNAs (circRNAs). Some of these circRNAs are expressed uniquely during reactivation or in distinct latency types where they likely play roles in the corresponding stages of the EBV infection cascade. By assessing viral circRNA expression across a broad range of cell types, latency types, reactivation, in vitro and in patient tumor samples, we have identified a small subset of EBV circRNAs that likely play fundamental roles in EBV biology EBV associated cancers. By performing a circRNAome analysis of the interspecies relative of EBV, the rhesus lymphocryptovirus, we found two of these to be evolutionarily conserved, indicating evolutionary constraints on maintaining their function. In this application, we will analyze the ubiquitiously expressed and conserved EBV circRNA, circRPMS1_E4_E3a. Our preliminary studies show that inhibition of circRPMS1_E4_E3a leads to decreased cell proliferation, indicating a fundamental phenotype in promoting cell growth. In this proposal, we propose three well integrated aims that will assess the fundamental mechanisms of circRPMS1_E4_E3a's interaction with chromatin and regulation of gene expression (aim 1), the influence of these interactions on modulating cell signaling (aim 2), and the link between its cell signaling responses and cell growth control (aim 3).

概括 EBV是一种人类肿瘤病毒，它是Headgkin淋巴瘤的病因，非霍奇金的淋巴瘤，胃癌和鼻咽癌，与之相关。在感染HIV的患者环境中。沿导致癌症的阶段阶段的进展，激活致癌途径的更多病毒基因。疱疹病毒的独特方面是它们对没有病毒的“潜伏期”基因表达程序的利用复制发生，仅表达了一小部分病毒基因，以重塑宿主细胞的胎儿促进病毒维持和持久性。与肿瘤形成所需的途径改变重叠，EBV潜伏基因是造成这种情况的关键因素肿瘤表型。由于非编码RNA不引起适应性免疫反应，因此使用病毒非编码RNA 潜伏期设置是维持体内病毒持久性并促进免疫力的关键疱疹策略清除。我们发现EBV表达了一类更大的非编码 RNA（CIRCRNA）。您可能在EBV感染级联的相关阶段中扮演角色在广泛的细胞类型，潜伏期类型，重新激活，体外和患者肿瘤中的circrna Expross 样本，我们已经确定了一小部分EBV circrnas，它们可能在EBV生物学中扮演基本角色 EBV相关的癌症。淋巴结病毒，我们发现其中两个是在进化中保守的，表明对上的进化约束维护其功能。 circrna，circrpms1_e4_e3a。降低细胞的序言，表明在该区块中促进细胞生长中的基本表型。提出三个综合目标，以评估CIRCRPMS1_E4_E3A'SSSS的基本机制与染色质的相互作用和基因表达的调节（AIM 1），相互作用对调节细胞信号传导（AIM 2），以及其细胞信号反应与细胞生长控制之间的联系（AIM 3）。