Function on Non-Coding RNA, MALAT1, in B-cell development and Lymphoma

非编码 RNA MALAT1 在 B 细胞发育和淋巴瘤中的作用

基本信息

批准号：
8784201
负责人：
Dinesh S Rao
金额：
$ 7.7万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8784201
关键词：
Affect Age American Animal Model B cell differentiation B-Cell Activation B-Cell Development B-Cell Lymphomas B-Cell NonHodgkins Lymphoma B-Lymphocytes Biological Biological Process Cell Lineage Cells Classification Clinical Data Development Developmental Process Diagnosis Disease Down-Regulation Drops Enzymes Future Gene Expression Generations Genes Genetic Recombination Goals Grant Health Human Immunoglobulin Class Switching Immunoglobulins In Vitro Incidence Interleukin-4 Lead Lipopolysaccharides Lymphocyte Lymphoma Lymphomagenesis MALAT1 gene Malignant Neoplasms Mature B-Lymphocyte Mediating MicroRNAs Molecular Mus Oncogenes Oncogenic Ontology Pathogenesis Pathologic Processes Patients Pattern Physiological Plasma Cells Play Population Prevalence Problem Solving Publications RNA RNA Sequences RNA Splicing Reaction Regulation Research Role Serine Staging Structure of germinal center of lymph node System Testing United States Untranslated RNA Work activation-induced cytidine deaminase base cancer type cohort human ARMET protein improved in vivo insight knock-down large cell Diffuse non-Hodgkin&apos s lymphoma loss of function novel novel strategies overexpression retroviral transduction transcriptome sequencing tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Human B-cell lymphoma is a significant clinical problem that is rising in incidence and prevalence as the American population ages. At the molecular level, changes in gene expression are central to both oncogenesis and developmental processes. Recently it has come to light that non-coding RNAs are central players in regulating gene expression. Extending our prior work in microRNAs, we now propose to analyze the contribution of a long non-coding RNA, Malat-1 to B-cell development and oncogenesis. Our preliminary data shows that Malat-1 is differentially regulated during the activation of B-cells, and recent publications implicate it as a target of activation-induced deaminase (AID), which can induce oncogenic translocations in germinal center B-cells. We therefore hypothesize that Malat1 may influence B-cell development and oncogenesis. Here, we propose to study the expression pattern of Malat1 in B-cell differentiation, and to understand its oncogenic function via gain and loss-of-function approaches in murine B-cells. These studies will delve into a novel, poorly understood field, as virtually nothing is known about long non-coding RNAs in B-cell lymphoma. In completing these aims, we will generate the necessary preliminary data to apply for a R01 grant. The completion of these goals promises to significantly increase our understanding of critical biological and pathological processes.

描述（由申请人提供）：人类B细胞淋巴瘤是一个重大的临床问题，随着美国人口年龄的增长，发病率和流行率正在增加。在分子水平上，基因表达的变化对于肿瘤发生和发育过程都是核心。最近，已经揭示了非编码RNA是调节基因表达的核心参与者。为了扩展我们在microRNA的先前工作，我们现在建议分析长的非编码RNA，malat-1对B细胞发育和肿瘤发生的贡献。我们的初步数据表明，在B细胞激活期间，MALAT-1受到差异调节，最近的出版物将其作为激活诱导的脱氨酶（AID）的靶标，这可以诱导生发中心B细胞中的致癌易位。因此，我们假设MALAT1可能会影响B细胞的发育和肿瘤发生。在这里，我们建议研究MALAT1在B细胞分化中的表达模式，并通过在鼠B细胞中的增益和功能丧失方法来理解其致癌功能。这些研究将深入研究一个新颖的，知之甚少的领域，因为对于B细胞淋巴瘤中的长期非编码RNA几乎一无所知。在完成这些目标时，我们将生成必要的初步数据以申请R01赠款。这些目标的完成有望大大提高我们对关键生物学和病理过程的理解。