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

摘要 人类B细胞淋巴瘤是一个重要的临床问题，其发病率和 随着美国人口的老龄化，这种疾病的流行程度也越来越高。在分子水平上，基因的变化 表达在肿瘤发生和发育过程中都是核心的。最近它 已经发现非编码RNA是调节基因的中心角色 表情。扩展我们以前在microRNAs方面的工作，我们现在建议分析 长非编码RNA Malat-1在B细胞发育和肿瘤发生中的作用。 我们的初步数据显示，Malat-1在激活过程中受到差异调节 B细胞，以及最近的研究表明它是激活诱导的脱氨酶的靶标 (AID)，它可以诱导生发中心B细胞的致癌易位。我们 因此，假设MALAT1可能影响B细胞的发育和肿瘤的发生。 在这里，我们建议研究MALAT1在B细胞分化中的表达模式，并 从功能获得和功能丧失两个方面了解其致癌功能 B细胞。这些研究将深入到一个新的、鲜为人知的领域，实际上 关于B细胞淋巴瘤中的长非编码RNA，目前还一无所知。在完成这些工作时 AIMS，我们将生成申请R01赠款所需的初步数据。这个 完成这些目标有望显著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.