冷诱导结合蛋白对脑胶质瘤发生发展的作用、机理及临床意义

cold-inducible RNA binding protein（ CIRP） is a secreted RNA binding protein which is involved in tumor development and drug resistance. However, the relationship between CIRP expression and malignant biological characteristics of glioma remains unknown. In previous study, we found expression pattern of CIRP could influence the growth, apoptosis and gene expression of nerve cells. In addition we first found that two major cold-inducible RNA binding proteins known as CIRP and RBM3 were aberrantly expressed in glioma tissue, the expression levels of them were elevated in high-grade gliomas versus low-grade or normal controls. So , in this study we plan to further understand the role of cirp in genesis and development of glioma ,and the molecular mechanism underlying: (1)Observation of the effect of CIRP expression on the biological feature of normal and transformed astrocytes; (2) Exploration of the mechanism of CIRP. The signal transduction pathways involved, and the downstream targeted genes will be observed. (3)Observation of the relationship between CIRP expression and the pathological grades of glioma , analysis of the possibility that cirp could be regarded as a new detection index. This project will shed light on the relationship between new gene function and malignant features of glioma, contribute to reveal the molecular mechanism of the occurrence and development of glioma accurately, and provide a new way for the individualized treatment of glioma.

冷诱导结合蛋白CIRP是一种分泌型的RNA结合蛋白，与肿瘤的发生发展及耐药相关。目前CIRP表达水平与胶质恶性生物学特征的关系，及其作用机理全世界尚无报道。本项目组前期的研究显示，CIRP的表达变化可影响神经细胞的生长、凋亡及基因表达情况。此外我们首次发现冷诱导休克蛋白家族成员在胶质瘤组织中异常表达，并随着胶质瘤恶性程度升高而升高。本研究拟在前期工作基础上，进一步深入研究CIRP在神经胶质瘤发生发展中的作用、机理及其临床意义：（1）观察CIRP表达变化对正常胶质及胶质瘤细胞生长行为的影响；（2）探讨CIRP调控胶质瘤发生、发展的机理。寻找其作用的下游靶分子；（3）观察CIRP表达水平与胶质瘤病理级别及预后的关系，分析其作为新型检测指标的可能性。该项目探索了新的基因功能改变与胶质瘤恶性特征的关系，为揭示胶质瘤发生发展的精确分子机制奠定了基础，为胶质瘤的个性化治疗提供新的思路。

神经胶质瘤是成人中枢神经系统中最常见的原发性肿瘤。然而目前有关胶质瘤发生、发展的机制，尤其是演变过程中的基因表达变化仍知之甚少。冷诱导结合蛋白CIRP是一种分泌型的RNA结合蛋白，与肿瘤的发生发展及耐药相关。目前CIRP表达水平与胶质恶性生物学特征的关系，及其作用机理全世界尚无报道。本项目深入研究了CIRP在神经胶质瘤发生发展中的作用、机理及其临床意义内容包括：（1）构建CIRP表达及干扰载体，以脑胶质瘤细胞系及正常大鼠神经胶质细胞为模型，利用体外细胞学实验及体内成瘤实验，研究CIRP表达变化对恶性胶质瘤发生、发展的影响；（2）探讨CIRP在胶质瘤发生、发展中发挥作用的途径。我们利用RNA结合蛋白免疫共沉淀技术及RNA测序技术，分析胶质瘤中与CIRP 蛋白发生结合的RNA（3）以临床病例为对象，观察CIRP表达水平与胶质瘤病理级别及预后的关系，分析其作为新型检测指标的可能性。结果发现CIRP表达水平与胶质瘤恶性程度的具有相关性，其CIRP表达变化对正常胶质及胶质瘤细胞的生长、迁移及耐药等一般生物学特性具有显著影响。CIRP 蛋白可以与特定的RNA结合从而发挥作用，CIRP蛋白有可能成为分子诊断的指标，既可使用肿瘤标本，也可以使用血清、脑脊液进行检测。该项目探索了新的基因功能改变与胶质瘤恶性特征的关系，为揭示胶质瘤发生、发展的分子机制奠定了基础，为胶质瘤的个性化治疗提供新的思路。