Laptm5作为ceRNA在小鼠B细胞淋巴瘤中的作用机制研究

miRNA通过结合mRNA的3'UTR区负调控靶基因的翻译。一个miRNA可识别多个mRNA的3'UTR 区。当不同mRNAs被同一个miRNA所调节时，这些mRNAs之间具有竞争性结合miRNAs的关系，被称为"竞争性内源RNAs（ceRNAs）"。本项目前期发现小鼠B细胞淋巴瘤中，c-Myc下调Laptm5，该蛋白可显著抑制淋巴瘤细胞增殖，但其机制不明。由于在Laptm5的3'UTR区含有几个miRNA的大量结合位点，可能对这些miRNA具有强大的吸纳作用，并因此对miRNA的其他靶蛋白产生影响，具有ceRNAs的作用。本研究拟通过芯片及生物信息学技术筛选B细胞淋巴瘤中与Laptm5具有共同miRNAs结合位点的mRNAs，利用报告基因实验验证Laptm5通过竞争性结合miRNA影响对相关mRNAs的转录后调控，并通过体内外实验探讨Laptm5在小鼠B细胞淋巴瘤中的作用机制。

MiRNAs negatively regulate gene expression by binding to 3 'untranslated regions of specific target mRNAs. A miRNA can recognize multiple target mRNAs. In this case, these target mRNAs competitively bind to the same miRNA and thus are called "competitive endogenous RNAs (ceRNAs). Our preliminary data indicates that Laptm5 is downregulated by oncogene c-Myc and inhibits the growth of both mouse and human lymphoma cells. Bioinformatics analysis shows Laptm5 3'UTR contains a large number of binding sites of different miRNAs, we hypothesize that laptm5 may have strong ceRNA effect to attract these miRNAs and increase the expression of their target genes. In this proposal, we plan to use our B-lymphoma models to screen target mRNAs that have the same miRNA binding sites as Laptm5 and define the role of Laptm5 as ceRNA to influence the post-transcriptional gene regulation. Our goal is to map the molecular pathways through which Laptm5 regulates lymphomagenesis and provide new targets for lymphoma treatment.