c-Myc诱导的长链非编码RNA CILR1促进肿瘤细胞有氧糖酵解的作用及机制研究

大量研究表明，肿瘤细胞的有氧糖酵解进程对肿瘤的发生发展至关重要。原癌基因c-Myc可通过转录调控大量编码蛋白基因促进有氧糖酵解，但对于c-Myc转录的长链非编码RNA是如何参与有氧糖酵解进而调控肿瘤发生发展的机制仍知之甚少。申请人前期研究发现c-Myc诱导的长链非编码RNA CILR1能促进肿瘤细胞的有氧糖酵解进程且特异性结合糖酵解限速酶HK2。因此提出假说：肿瘤细胞中c-Myc→CILR1→HK2信号通路通过促进有氧糖酵解进程发挥促癌作用。本项目将在已有的工作基础上，利用分子生物学和细胞生物学实验方法深入研究上述信号通路对肿瘤细胞有氧糖酵解的促进作用及具体分子机制；通过小鼠异种移植瘤模型和生物信息学分析TCGA数据库等阐明CILR1与肿瘤发生发展的相关性。本项目的进行有助于从长链非编码RNA这一角度完善c-Myc与肿瘤有氧糖酵解之间的调控网络，从而为肿瘤治疗提供新的理论依据和潜在靶点。

A large number of studies have shown that the aerobic glycolysis process of tumor cells is very important for the occurrence and development of tumor. The proto-oncogene c-Myc can promote aerobic glycolysis through transcriptional regulation of many protein-coding genes. However, little is known about the mechanism of how c-Myc transcribed long non-coding RNA participates in aerobic glycolysis to regulate the occurrence and development of tumors tumor development. Our previous study found that c-Myc-induced long non-coding RNA CILR1 can promote the aerobic glycolysis process of tumor cells, and specifically bind to the glycolysis rate limiting enzyme HK2. Therefore, we hypothesized that the c-Myc→CILR1→HK2 signaling pathway in tumor cells plays a carcinogenesis role by promoting the aerobic glycolysis process. Based on the existing work, this project will adopt experimental methods on molecular biology and cell biology to deeply study the promoting effect of the above signaling pathway on aerobic glycolysis of tumor cells, as well as the detailed molecular mechanism. Moreover, the correlation between CILR1 and tumor occurrence and development would be clarified through the mouse xenotransplantation tumor model and bioinformatics analysis of TCGA database. The implementation of this project helps to improve the regulatory network between c-Myc and aerobic glycolysis of tumors from the perspective of long non-coding RNA, thus providing new theoretical bases and potential targets for tumor therapy.