代谢应激诱导lncRNA MITA1通过调控IL-7的表达在胶质母细胞瘤发生发展中的作用及机制研究

胶质母细胞瘤（GBM）致死致残率高，是严重危害人类生命健康的颅内恶性肿瘤。研究发现，lncRNA在GBM的发生发展中至关重要。而耦联肿瘤代谢的lncRNA MITA1作为潜在靶标，其与GBM的关系没有报道。预实验结果发现：MITA1表达在葡萄糖饥饿的GBM细胞中显著升高；抑制MITA1显著阻碍GBM细胞的迁移和侵袭；MITA1可正向调控IL-7，且之间存在RNA-RNA互作；IL-7与GBM预后呈负相关。由此我们推测：MITA1可通过IL-7调控GBM发生发展。为证实此设想，拟开展如下研究：1）明确MITA1在GBM中的表达及其临床相关性；2）揭示MITA1在GBM发生发展中的功能；3）阐明MITA 1调控GBM的分子机制。本项目有望揭示一个耦联代谢的全新lncRNA参与GBM发生发展的调控网络，为GBM的预防、诊断和治疗提供新的靶点和思路，具有重要的理论意义和临床转化价值。

Glioblastoma (GBM) is a common intracranial malignant tumor that seriously endangering human lives and health, with high disability and death rates. Currently, the standard treatment of GBM is maximal safe surgical resection, followed by radiation therapy and concomitant temozolomide (TMZ) and then adjuvant TMZ. Despite considerable effort, little progress has been made toward prolonged survival in GBM. Long noncoding RNA (lncRNA) expression can be associated with tumor development, progression and can be used as a therapeutic target in GBM. Our previous studies have shown that lncRNA MITA1 is critical for the metastatic phenotype of hepatocellular carcinoma. As a potential target, MITA1 coupled with tumor metabolism has not been reported in relation to GBM. Our pilot experiments suggested that the expression of MITA1 was significantly increased in glucose-starved GBM cells. Moreover, inhibition of MITA1 significantly inhibited the migration and invasion of GBM cells. MITA1 can positively regulate IL-7, and there is RNA-RNA interaction between them. In addition, we found that IL-7 was negatively correlated with prognosis in GBM. In consequences, we according to these results speculated that MITA1 could regulate the development of GBM through IL-7. To prove this hypothesis, the following studies are planned. Firstly, we will examine the expression of MITA1 in the GBM, and analyze the correlation between MITA1 expression and GBM clinical features, to establish the link between each other. We therefore next modulated the expression of MITA1, via over-expression and shRNA-mediated knockdown, to determine the function of MITA1 in GBM. Thirdly, we will elucidate the molecular mechanism and their regulatory axis in GBM pathogenesis underlying the regulation by MITA1of the IL-7 expression. This project is expected to establish a new regulatory network of metabolic related lncRNA participating in the occurrence and development of GBM, and which could provide new targets and new ideas for the prevention, diagnosis and treatment of GBM.