能量代谢异常是肿瘤细胞恶性转变的重要生物学特征。miRNAs作为重要的调控因子，在肿瘤细胞能量代谢过程中如何发挥调控作用是当前的研究热点。本项目组前期筛选发现，miR-375作为近期报道的血糖调控相关miRNA，在肝癌细胞中表达显著降低，并有4个潜在靶点可调控线粒体能量代谢的关键步骤。由此我们推测,miR-375极有可能通过调控线粒体功能进而影响肝癌细胞能量代谢水平。基于上述设想，本项目拟：①利用多种肝癌细胞株及裸鼠荷瘤模型，明确miR-375表达水平对肝癌细胞能量代谢的影响；②采用报告基因、miRNA表达调控、RNA及蛋白检测技术验证miR-375与4个靶基因（PDHK1、LDHB、ACSL4和OCNT1）的调控关系；③进一步通过调控miR-375表达水平检测其对线粒体内能量代谢通路的影响。本项目的完成将为探究肝癌线粒体能量代谢的调控机制奠定新的理论基础，亦为肝癌靶向治疗提供新的思路。

Abnormal energy metabolism is an extremely important indicator of malignant transformation. As important regulatory factors, miRNAs have become a major focus in research on the regulation of energy metabolism in tumor cells. miR-375, as a member of the miRNA family, has been reported to be related to glucose metabolism. Our previous screening study of miRNAs showed that the expression of miR-375 was significantly reduced in hepatocellular carcinoma and that miR-375 had four potential targets that might play a regulatory role in the core steps of mitochondrial energy metabolism. Therefore, we speculate that miR-375 may have a significant effect on the regulation of abnormal energy metabolism in the liver, which has not yet been studied worldwide. Based on the above assumption, this project is aimed to: ① demonstrate the impact of the miR-375 expression level on energy metabolism in hepatocellular carcinoma by using a variety of hepatocellular carcinoma cell lines and their models in nude mice; ② identify the regulatory relationship between miR-375 and the four target genes ( PDHK1, LDHB, ACSL4 and OCNT1 ) with the help of the technologies such as the gene reporter, the regulation of the miRNA expression, and the RNA and protein detection techniques; ③ explore the influence of miRNA on the pathway of mitochondrial energy metabolism by further regulating its expression level. This project is expected to lay a theoretical foundation for the mechanism by which hepatic mitochondrial energy metabolism is regulated, and to provide new directions in the targeted therapy for hepatocellular carcinoma.