MCT-1 作为弥漫性大B细胞淋巴瘤治疗靶点及机制研究

项目名称： MCT-1 作为弥漫性大B细胞淋巴瘤治疗靶点及机制研究

项目编号： No.31271496

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 戴博杰

作者单位： 同济大学

项目金额： 80万元

中文摘要： 癌基因MCT-1 (Multiple copies in T-cell lymphoma-1)与淋巴瘤的发病密切相关。体外实验显示，MCT-1具有抑制细胞凋亡，提高细胞增殖和促进血管生成等多方面的功能，但是，尚未通过体内实验证实。本研究将建立 MCT-1转基因小鼠模型，并用该模型研究MCT-1在淋巴瘤发病中的作用和分子机制。同时，利用RIP-CHIP技术系统研究MCT-1在弥漫性大B细胞淋巴瘤（DLBCL）中翻译水平上的调控。此外，我们最近的实验结果表明，MCT-1在人类绝大多数的DLBCL中高表达，基因敲除掉MCT-1诱导了细胞凋亡。这提示MCT-1可能是DLBCL新的治疗靶点。本研究将设计MCT-1特异的抑制剂来阻断MCT-1的功能，然后利用细胞和小鼠肿瘤异体移植模型探讨其对DLBCL的治疗效果和毒副作用。我们的研究结果将为DLBCL的治疗提供重要的理论依据和新的有效途径。

中文关键词： 弥漫大B淋巴瘤；MCT-1；癌基因；PKC抑制剂；凋亡

英文摘要： Oncogene MCT-1(Multiple copies in T-cell lymphoma-1) stimulates cell proliferation, suppresses apoptosis, promotes angiogenesis and modulates the translation of cancer-related genes. In vitro studies supported its role in lymphomagenesis. However, it has not been testified in vivo. In this study, we will establish a MCT-1 transgenic mouse model to investigate the role of MCT-1 and its molecular mechanism in lymphomagenesis. Meanwhile, RIP-CHIP assay will be used to globally study the mRNAs modulated by MCT-1 in Diffuse Large B-cell Lymphoma (DLBCL). Moreover, our recent data have shown that MCT-1 is elevated in the majority of human DLBCL samples and knocking down MCT-1 by shRNA induces apoptosis in DLBCL cells, supporting its value as a potential therapeutic target for DLBCL. A specific MCT-1 inhibitor will be designed to disrupt MCT-1 function. The therapeutic effect of the MCT-1 peptide inhibitor will be investigated in cell culture system and mouse xenograft models. This study will provide important evidence and a new approach for DLBCL treatment.

英文关键词： DLBCL；MCT-1；oncogene；PKC inhibitor；apoptosis