Alternative Cleavage and Polyadenylation Events as Biomarkers

作为生物标志物的替代切割和聚腺苷酸化事件

• 批准号: 8600659
• 负责人: ERIC J WAGNER
• 金额: $ 7.37万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8600659
• 关键词: 3' Untranslated Regions; Area; Attenuated; B-Lymphocytes; Biological Assay; Biological Markers; Biology; CCND1 gene; Candidate Disease Gene; Cells; Cessation of life; Chromosome abnormality; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Data; Diagnosis; Diagnostic; Disease; Distal; Enhancers; Event; Genetic Transcription; Genome; Goals; Investigation; Laboratories; Lead; Length; Light; Longitudinal Studies; Lymphoma; Malignant Neoplasms; Mantle Cell Lymphoma; Measures; Mediating; Messenger RNA; MicroRNAs; Molecular Profiling; Mutation; Non-Hodgkin' s Lymphoma; Patients; Phase Transition; Poly A; Polyadenylation; Positioning Attribute; Process; Proteins; RNA Interference; Repression; Research; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Role; S Phase; Screening for cancer; Site; Technology; Testing; Transcript; Transcriptional Activation; Translations; Up-Regulation; Variant; anticancer research; cancer type; deep sequencing; design; information gathering; member; mortality; outcome forecast; overexpression; public health relevance; tumorigenesis

DESCRIPTION (provided by applicant): A hallmark event in the formation of Mantle Cell Lymphoma (MCL) is the translocation of the cyclin D1 gene downstream of the Ig Enhancer resulting in an upregulation of transcription. In the most proliferative cases of MCL in patients with the lowest survival the cyclin D1 3'UTR is shortened through alternative cleavage and polyadenylation (APA) resulting in a more stable mRNA that is resistant to microRNA. We will also using the newly developed 3P-Seq Deep Sequencing technology to define a global polyA site selection signature for MCL. Also, we will systematically deplete the known members of the cleavage and polyadenylation machinery and test for changes in cyclin D1 poly(A) site selection. Collectively, the information gathered from this proposal will provide a clearer picture of APA events both at the cyclin D1 locus and throughout the genome. This will provide further diagnostic markers and may aid in early cancer detection.

描述（由申请人提供）：套细胞淋巴瘤（MCL）形成的标志性事件是细胞周期蛋白D1基因在IG增强子下游的易位，导致转录上调。在具有最低存活率的MCL的最增殖病例中，细胞周期蛋白D1 3 'UTR通过交替切割和多聚腺苷酸化（阿帕）缩短，从而产生对microRNA具有抗性的更稳定的mRNA。我们还将使用新开发的3 P-Seq深度测序技术来定义MCL的全局polyA位点选择签名。此外，我们将系统地耗尽已知的成员的切割和多聚腺苷酸化机制和测试的变化，在细胞周期蛋白D1聚（A）位点的选择。总的来说，从本提案中收集的信息将提供一个更清晰的画面， 阿帕事件在细胞周期蛋白D1基因座和整个基因组。这将提供进一步的诊断标志物，并可能有助于早期癌症检测。