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

摘要 人B细胞淋巴瘤是一个重要的临床问题，其发病率正在上升， 随着美国人口的老龄化，在分子水平上， 表达是肿瘤发生和发育过程的中心。最近它 已经发现非编码RNA是调控基因的核心角色， 表情扩展我们先前在microRNA方面的工作，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，Malat-1在激活 B细胞，最近的出版物暗示它是活化诱导脱氨酶的靶点 (AID)，其可诱导生发中心B细胞中的致癌易位。我们 因此，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， 在小鼠中通过获得和丧失功能的方法来了解其致癌功能， B细胞这些研究将深入到一个新的，知之甚少的领域，因为几乎 对于B细胞淋巴瘤中的长链非编码RNA还一无所知。在完成这些 为了达到这一目标，我们将提供申请R 01补助金所需的初步数据。的 这些目标的完成将大大提高我们对关键问题的理解。 生物和病理过程。

ABSTRACT 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.