长链非编码RNA（lncRNA）在脑胶质瘤的发生发展中具有重要作用。申请人前期研究发现在脑胶质瘤组织及细胞系中lncRNA TMEM44-AS1表达上调，并且其高表达预示着病人更差的预后。敲减TMEM44-AS1抑制胶质瘤细胞增殖和侵袭，同时也抑制TGFβR1的表达。此外，TMEM44-AS1在脑胶质瘤中激活与超级增强子有关，敲减增强子招募因子MED1显著抑制TMEM44-AS1的表达。本项目拟在以往研究工作的基础上，采用RNAi、荧光素酶报告基因及ChIP-PCR等技术以及超级增强子抑制剂，将临床样本、体外胶质瘤细胞株与体内裸鼠原位移植瘤模型相结合，研究TMEM44-AS1对胶质瘤细胞增殖和侵袭的影响，并调查其分子机制，以及探讨超级增强子调控TMEM44-AS1对胶质瘤恶性表型的影响。我们相信该项目的开展对揭示胶质瘤发病的分子机制，合理设计与开发胶质瘤治疗的靶标分子具有重要的意义。

Long non-coding RNA (lncRNA) plays an important role in the development of glioma.Our previous study showed that the expression level of lncRNA TMEM44-AS1 was upregulated in glioma tissues and cell lines, and its high expression can be taken as an index of a worse prognosis for the patient with glioma. Knockdown of TMEM44-AS1 inhibited proliferation and invasion of glioma cells and also inhibited TGFβR1 expression. In addition, TMEM44-AS1 activation in gliomas was associated with super enhancers. Our work indicated that knockdown of MED1, a recruiting factor of enhancer, significantly inhibited TMEM44-AS1 expression. Based on our previous work, this project will combine with clinical samples, in vitro glioma cell lines and in vivo nude mouse orthotopic tumor model by RNAi, luciferase reporter gene, Chip-PCR technology and super enhancer inhibitor to study the effects of TMEM44-AS1 on the malignant phenotypes such as proliferation and invasion of glioma cells, and investigate its molecular mechanism, and explore the effect of super-enhancer regulation of TMEM44-AS1 on the malignant phenotype of glioma. We believe this project is important for further revealing the molecular mechanism of gliomas pathogenesis, and improving the rational design of therapeutic drugs for the treatment of gliomas.