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

基本信息

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
项目类别：
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&apos 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&apos 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

项目摘要

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）形成的一个标志性事件是 Ig 增强子下游的细胞周期蛋白 D1 基因易位，导致转录上调。在存活率最低的患者中增殖最严重的 MCL 病例中，细胞周期蛋白 D1 3'UTR 通过选择性切割和多聚腺苷酸化 (APA) 被缩短，从而产生更稳定的 mRNA，对 microRNA 具有抗性。我们还将使用新开发的3P-Seq深度测序技术来定义MCL的全局polyA位点选择特征。此外，我们将系统地耗尽已知的切割和聚腺苷酸化机制成员，并测试细胞周期蛋白 D1 Poly(A) 位点选择的变化。总的来说，从该提案中收集的信息将提供更清晰的情况细胞周期蛋白 D1 位点和整个基因组的 APA 事件。这将提供进一步的诊断标记，并可能有助于早期癌症检测。