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

描述（由申请人提供）：人类B细胞淋巴瘤是一个重要的临床问题，随着美国人口的老龄化，其发病率和患病率正在上升。在分子水平上，基因表达的变化是肿瘤发生和发育过程的中心。最近，人们发现非编码RNA是调节基因表达的核心参与者。扩展我们先前在microRNA方面的工作，我们现在建议分析长非编码RNA Malat-1对B细胞发育和肿瘤发生的贡献。我们的初步数据显示，Malat-1在B细胞活化过程中受到差异调节，最近的出版物暗示它是活化诱导脱氨酶（AID）的靶点，AID可以诱导生发中心B细胞的致癌易位。因此，我们假设Malat 1可能影响B细胞发育和肿瘤发生。在这里，我们建议研究Malat 1在B细胞分化中的表达模式，并通过小鼠B细胞中功能获得和丧失的方法来了解其致癌功能。这些研究将深入到一个新的，知之甚少的领域，因为几乎没有什么是已知的长非编码RNA在B细胞淋巴瘤。在完成这些目标，我们将产生必要的初步数据，申请R 01补助金。这些目标的完成有望大大增加我们对关键生物和病理过程的理解。

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.