肺癌脑转移是最常见的脑转移肿瘤，患者的预后差。我们检测肺癌原发瘤和脑转移瘤环状RNA和微小RNA表达谱发现脑转移瘤中circESPL1显著升高、miR451a显著下调。体外研究发现circESPL1 siRNA抑制肺癌细胞增殖和侵袭，且circESPL1靶向结合miR451a进而上调原癌基因Myc表达。因此设想circESPL1通过调控miR451a/Myc促肺癌脑转移。本研究将检测肺癌脑转移瘤circESPL1、miR451a的表达，分析其与患者临床病理特征及预后的关系；并利用定量PCR等方法通过体外实验及肺癌脑转移裸鼠模型对circESPL1调控肺癌细胞脑转移的机制做深入研究。本研究将揭示circESPL1调控miR451a/Myc促肺癌脑转移的分子机制，从而为肺癌脑转移防治提供新靶点。

Brain metastatic disease from lung cancer (LC) is the most frequent in brain metastatic tumor, and lung cancer associated with brain metastasis indicates poor prognosis. We found that the expression of circESPL1 is significantly upregulated in brain metastatic tissues compared with primary tumor of lung cancer. In vitro assays showed that silencing of circESPL1 significantly suppressed proliferation and invasion of lung cancer cells. Furthermore, bioinformatics and dual-luciferase analysis found that circESPL1 can combine competitively with miR451a and upregulate the expression of oncogene Myc. On this basis, we hypothesis that circESPL1 will promote brain metastatic LC through regulating miR451a/Myc. We will detect the expression of circESPL1 and miR451a in a large number of brain metastatic LC, analyze the relationship with clinical pathological characteristics and prognosis of patients. We will further investigate the possible mechanism of circESPL1 regulating brain metastatic LC using both in vitro quantitative PCR method and a brain metastatic nude mice model. Our study will clarify the molecular mechanism that circESPL1 promotes brain metastatic LC through regulating miR451a/Myc and provide a new target on prevention and treatment of brain metastatic LC.