新的干扰素调节因子3可变剪接体与肿瘤的相关性及其在肿瘤预后判断中作为分子标志物的可能性

项目名称： 新的干扰素调节因子3可变剪接体与肿瘤的相关性及其在肿瘤预后判断中作为分子标志物的可能性

项目编号： No.30871366

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 李勇

作者单位： 北京市肿瘤防治研究所

项目金额： 29万元

中文摘要： 干扰素调节因子3(IRF-3)是宿主细胞抗病毒反应的早期应答基因，可诱导多种免疫调节相关基因的表达，并激活延迟抗病毒免疫反应。作为抑癌基因，IRF-3可抑制肿瘤细胞的生长和转移，并诱导病毒感染细胞的凋亡。其可变剪接体形式IRF-3a可通过抑制IRF-3的功能发挥癌基因的作用。本课题组从肿瘤细胞中克隆了6种新的IRF-3可变剪接体，证实其中5种在食管癌、宫颈癌和肝癌组织中呈肿瘤特异性表达趋势，并进一步证实该5种可变剪接体可不同程度地抑制IRF-3对干扰素βFNβ#21551;动子的转录激活功能。目前以下几个方向亟需研究：①#26032;发现的可变剪接体抑制IRF-3功能的分子机制；②#26032;发现可变剪接体的细胞生物学功能及分子机制；③#26032;发现的可变剪接体及其重要生物学功能的作用相关基因用于肿瘤预后判断的可能性。该领域的深入研究有利于阐明IRF-3及可变剪接体与肿瘤的相关性及其在肿瘤预后判断中作为分子标志物的可能性。

中文关键词： 干扰素调节因子3; 可变剪接体; 肿瘤标志物; 预后判断.

英文摘要： Interferon regulatory factor 3 (IRF-3) is an immediate-early response gene in the host innate immune response against viral infection and plays critical roles in the subsequent activation of adaptive immunity. In addition to its role in microbial defense, IRF-3 is identified to act as a tumor suppressor gene and play a negative control role in tumor cell growth and metastasis and induce apoptosis of virus-infected cells. IRF-3a is an alternative splicing variant of IRF-3 and is suggested to facilitate oncogenic transformation through suppressing IRF-3 activity. Here we isolated 6 novel splicing variants encoded by IRF-3 gene from tumor cells and showed that 5 novel variants mainly express in tumor tissues compared with the distanced normal tissues in esophagus cancer, cervical cancer and hepatocellular carcinoma. Further study confirmed that these 5 novel variants, to different extent, inhibit the transcriptional activation of IRF-3 on IFNβromoter. Thus, the following contents are awaiting further investigation: ①The molecular mechanism for the inhibitory function of novel splicing variants on IRF-3 activity; ②The cellular biological function of novel splicing variants and the related molecular mechanism; ③The possibility for novel splicing variants and their functionally related genes acting as tumor marker for prognosis. Further research work in this field is helpful to elucidate the correlation between novel IRF-3 splicing variants and tumor and the possibility as molecular marker for tumor prognosis.

英文关键词： Interferon regulatory factor 3; alternative splicing variant; tumor marker; prognosis.