FLI1环状RNA在小细胞肺癌发生发展中的作用及分子机理

Small cell lung cancer (SCLC) has the most malignant degree and worst prognosis among lung cancer. We have found that Friend leukemia virus integration 1 （FLI1） is highly expressed in SCLC tissue, and the expression level of FLI1 is positively correlated with the malignant phenotype of SCLC. Meanwhile,we have discovered that there is FLI1 circular RNA (FLI1 circRNA) in SCLC cells, and the circRNA could bind the regulation region of FLI1 promoter. Based on the previous studies, we propose a novel regulatory hypothesis that FLI1 circRNA is invovlved in the function of FLI1 in the carcinogenesis of SCLC. Thus,this project will reveal a novel mechanism of FLI1 circRNA in the regulation of FLI1 and other genes expression through reverse transcription associated trap assay (RAT),deep sequencing, chromosome conformation capture(3C) and chromatin immunoprecipitation(ChIP) etc, in order to clarify the mechanism of FLI1 circRNA invovled in the development of SCLC and to provide the new concept and experimental basis for the study of molecular biomarkers and target therapy in SCLC.

小细胞肺癌（SCLC）是肺癌中恶性程度最高、预后最差的类型。我们前期工作提示FLI1高表达与SCLC恶性表型密切相关，并发现SCLC细胞中存在FLI1环状RNA（circRNA），其能与FLI1等基因启动子调控区相结合，国内外尚未见相关报导。本项目拟基于前期工作基础，探讨FLI1 circRNA参与FLI1促癌调控机制的全新假设，应用逆转录相关捕获法（RAT）、高通量测序、染色质空间构象捕获法（3C）、染色质免疫共沉淀法(ChIP)等技术揭示FLI1 circRNA调控FLI1等基因转录的机制，阐明其在SCLC发生发展中的作用及机理，为SCLC分子标志物及靶向治疗研究提供新的思路与实验基础。