胶质瘤是颅内最常见的恶性肿瘤，也是神经外科和肿瘤科学研究领域面临的世界性难题。能量代谢方式的改变是胶质瘤等恶性肿瘤的重要生物学特征之一，抑制其特异性的代谢途径/代谢产物的生成能够有效阻止其生长，但其调节机制有待进一步研究。许多研究表明microRNA是能量代谢的重要调控因子。本项目是在对胶质瘤microRNA差异表达筛查的基础上，首次提出胶质瘤中miR-125a-5p通过直接或间接调控能量代谢的关键酶以及代谢通路进而抑制肿瘤发生发展的假说；拟检测miR-125a-5p在不同级别胶质瘤组织、血液及脑脊液中的表达；在体外和体内模型上证实miR-125a-5p影响胶质瘤能量代谢和肿瘤生物学行为的作用；结合生物信息学和代谢组学的方法，探讨miR-125a-5p调控胶质瘤能量代谢的机制；本研究将会对揭示胶质瘤能量代谢调控的新机制和理解其他肿瘤与能量代谢的关系提供新思路。

Gliomas are the most common types of malignant brain tumors and global difficult problems in the neurosurgical and oncological fields. The change in the way of energy metabolism is one of the most important biological characteristics of gliomas. The inhibition of the specific metabolic pathways and production of metabolites may effectively prevent the glioma growth. However, its regulatory mechanisms remain answered, and it still needs further investigation. Many studies have indicated that microRNA is an important regulatory factor of the energy metabolism. Based on screening the differentially expressed miR-125a-5p in glioblastoma, we will for the first time test the hypothesis that miR-125a-5p in gliomas could promote the initiation and development of gliomas via direct and indirect regulation of the critical regulatory enzymes of energy metabolism and metabolic pathways. We also shall determine the expression of miR-125a-5p in the tissues,blood and CSF of patients with the different grades of gliomas. We will then validate whether miR-125a-5p could influence glioma energy metabolism and biological behaviors in vitro and in vivo models. We will explore the molecular mechanisms of miR-125a-5p on regulation of glioma energy metabolism via the combinational approach of bioinformatics and metabolomics. This study will provide novel insights into the new regulatory mechanisms of energy metabolism in gliomas and understanding the association between other tumors and energy metabolism.