PCBP2和miR-151-5p/miR-16共同调节RhoGDIA表达影响神经胶质瘤的转移和侵袭

项目名称： PCBP2和miR-151-5p/miR-16共同调节RhoGDIA表达影响神经胶质瘤的转移和侵袭

项目编号： No.31301152

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 韩为

作者单位： 中国医学科学院基础医学研究所

项目金额： 23万元

中文摘要： 恶性神经胶质瘤在临床上治疗效果、预后差，生存率低。深入研究神经胶质瘤发生和发展过程中调控机制，为开发新药物靶标，指导临床用药及预后判断提供理论基础。近年来RNA结合蛋白、微小RNAs及其靶mRNA之间的相互作用成为研究热点。本项目在前期工作中发现PCBP2作为潜在的原癌基因促进胶质瘤细胞增殖，抑制凋亡。我们利用RIP-chip， pull-down等技术筛选和鉴定了与PCBP2结合的靶mRNA之一-RhoGDIA。通过生物信息学分析，发现与RhoGDIA mRNA 3'UTR区结合的PCBP2和miR-151-5p/miR-16结合位点具有非常密切的空间关系。本项目在上述工作基础上将研究PCBP2和miR-151-5p/miR-16协同作用于RhoGDIA的3'UTR区，调节该基因的表达并进一步影响肿瘤的增殖、浸润和转移。该工作将揭示RNA结合蛋白-微小RNA-mRNA之间新的调控网路。

中文关键词： 神经胶质瘤；RhoGDIA；PCBP2；侵袭；微小RNA

英文摘要： Until recently, the effect of clinical treatment on malignant gliomas has a poor prognosis and very low survival rates. In-depth study of the regulation mechanism in the occurrence and development of glioma will provide a theoretical basis for the exploration of new drug targets, guiding clinical treatment and prognosis judgement. In recent years, the research on interaction among RNA binding proteins, microRNAs and their target mRNAs has become a hotspot. In our previous work, it was found that a role for the potential proto-oncogene PCBP2 in the growth and survival of gliomas, knockdown of PCBP2 inhibits glioma growth in vitro and in vivo through inhibiting of cell cycle progression and inducing of apoptosis. RhoGDIA was identified as a target mRNA binding to PCBP2 through RIP-chip and biotin pull-down. With bioinformatics analysis, we also found a very close relationship between PCBP2 binding to RhoGDIA-3?UTR and the seed sequence sites of miR-151-5p/miR-16. Based on the previous work, this study will focus on that the cooperative effect of PCBP2 and miR-151-5p/miR-16 on the RhoGDIA-3?UTR modulates the gene expression, furtherly affecting the proliferation, invasion and metastasis of glioma. This work will reveal a new regulatory network on RNA binding proteins, microRNAs and their target mRNAs.

英文关键词： Glioma；RhoGDIA；PCBP2；Invasion；microRNA