结直肠癌是威胁人类健康的重大疾病，限制饮食可以抑制肿瘤的恶性进程，因此，深入探讨限制饮食通过能量代谢抑制结直肠癌恶性进程的具体机制，有助于优化围术期饮食管理。我们的前期工作发现限制饮食介导了结直肠癌细胞糖酵解异常，且胆固醇合成酶FDFT1（法尼基二磷酸法尼基转移酶1）表达升高；FDFT1过表达可抑制结直肠癌细胞增殖，干预FDFT1后蛋白质组学发现糖酵解通路、翻译起始因子eIF4F复合物被显著富集，其中糖酵解关键酶GPI被限制饮食和FDFT1调控。我们推测限制饮食上调FDFT1表达后通过eIF4F复合物介导GPI mRNA翻译异常调控糖酵解，抑制结直肠癌的增殖。本项目拟采用基因沉默等技术进行限制饮食通过FDFT1抑制结直肠癌增殖的体内外功能研究，探索FDFT1对GPI及糖酵解通路的翻译水平调控模式，阐明限制饮食抑制结直肠癌恶性进程的机制，为优化结直肠癌患者围术期饮食管理提供理论依据和新思路。

Colorectal cancer is a major threaten to human health, the prognosis of patients after surgery is still poor, so it is particularly important to strengthen the perioperative management. Fasting can inhibit the malignant progression of many kinds of tumors and glycolysis is the main energy source of tumor dependence. Therefore, in-depth study of the specific mechanism of fasting through energy metabolism inhibiting the malignant progression of colorectal cancer is helpful to optimize the perioperative diet management and improve the prognosis. Our previous work found that fasting can mediate colorectal cancer cell glycolysis abnormality, and up-regulate the expression of cholesterol biosynthesis enzymes FDFT1 (Farnesyl-Diphosphate Farnesyltransferase 1). Overexpression of FDFT1 can inhibite the proliferation of colorectal cancer cells. Proteomics analysis found that the glycolytic pathway and eIF4F complex (Eukaryotic Translation Initiation Factor 4F complex) were significant enriched after intervention in FDFT1. The key glycolytic enzymes GPI (Glucose-6-Phosphate Isomerase) was regulated by fasting and FDFT1. Accordingly, we put forward the hypothesis that fasting can up-regulation FDFT1 which through eIF4F complex mediate GPI mRNA translation abnormality then influence glycolysis, and inhibit the proliferation of colorectal cancer. In this study, gene silencing was used to study the effects of fasting on colorectal cancer proliferation through FDFT1 in vivo and in vitro, to explore the translation-level regulation mode of FDFT1 on GPI and glycolysis pathway, to clarify the mechanism of fasting inhibition of malignant progression of colorectal cancer and to provide theoretical basis and new ideas for optimizing perioperative diet management in patients with colorectal cancer.