FLI1环状RNA编码小肽在胶质母细胞瘤中的作用和机制研究

Glioblastoma multiforme (GBM) has the most malignant degree and worst prognosis among brain glioma. We have discovered that Friend leukemia virus integration 1（FLI1）is highly expressed in GBM tissue, and FLI1 expression level is positively correlated with the malignant phenotype and poor prognosis of GBM. Ulteriorly, we have innovatively found that there is FLI1 circular RNA (FLI1 circRNA，cFLI1) in GBM cells, and cFLI1 could translate small peptide to regulate the expression of parental gene mRNA. Based on the previous studies, this project will analysis the correlation of the cFLI1 small peptide and clinical characteristics and prognosis of GBM via detection of tissue samples; detect the effect of cFLI1 small peptide on cell growth, cycle, apoptosis and migration in cell and animal level, clarifying the mechanism of this small peptide involving in the development of GBM; reveal a novel mechanism of cFLI1 small peptide in the regulation of FLI1 linear mRNA through deep sequencing, chromatin immunoprecipitation(ChIP) and dual luciferase reporter system etc, in order to provide a novel concept and experimental basis for the study of molecular biomarkers and target therapy in GBM.

胶质母细胞瘤（GBM）是脑胶质瘤中恶性程度最高、预后最差的类型。我们近期的研究工作提示FLI1在GBM组织中高表达，并与其恶性表型及不良预后密切相关。此外，我们还创新性地发现GBM细胞中存在FLI1环状RNA（FLI1 circRNA，cFLI1），cFLI1可通过编码小肽影响其亲本基因mRNA的转录。本项目拟基于前期工作基础，通过对临床组织标本的检测明确cFLI1小肽与GBM临床特征及预后的相关性；在细胞及动物水平检测cFLI1小肽对GBM细胞生长、周期、凋亡及迁移等恶性表型的影响，阐明其在GBM发生发展中的作用；应用高通量测序、染色质免疫共沉淀法(ChIP)及双荧光素酶报告系统等技术揭示cFLI1小肽调控FLI1亲本基因mRNA转录的具体机制，为GBM分的子标志物及靶向治疗研究提供新的思路和实验基础。

胶质母细胞瘤（GBM）是脑胶质瘤中恶性程度最高、预后最差的类型。我们近期的研究工作提示FLI1在GBM组织中高表达，并与其恶性表型及不良预后密切相关。此外，我们还创新性地发现GBM细胞中存在FLI1环状RNA（FLI1 circRNA，FECR），FECR可通过编码小肽影响其亲本基因mRNA的转录。本项目通过对临床组织标本的检测明确了FECR小肽与GBM临床特征及预后的相关性；在细胞水平检测证实cFLI1小肽对GBM细胞生长、周期、凋亡及迁移等恶性表型的影响，说明其在GBM发生发展中的关键作用；应用IP-MS技术，明确与FECR小肽发生相互作用的蛋白SLFN5，并证实其可通过与SLFN5的相互作用，调控下游促癌基因的转录，为GBM发病机制的探索提供了新的思路。