代谢重编程和细胞周期调控异常是肿瘤的两个重要特征，两者之间如何交互作用以促进肿瘤发生发展目前尚不清楚。我们前期研究发现，脂代谢重编程酶—长链脂酰辅酶Ａ合成酶4(ACSL4)在肝癌中显著高表达，并与不良预后密切相关。抑制ACSL4表达能下调cMyc水平并诱导肝癌细胞发生G1/S期阻滞，然而作用机制尚不清楚。本研究拟分析肝癌组织中ACSL4/cMyc的表达水平与临床病理特征和预后的相关性；明确ACSL4的表达变化对肝癌细胞增殖能力的影响，应用生物信息学、免疫共沉淀、泛素化及截短等技术阐明ACSL4通过FBW7调控cMyc稳定性促肝癌增殖的分子机制；采用裸鼠肝癌模型、尾静脉注射模型、PDX模型从体内研究ACSL4对肝癌细胞成瘤及转移能力的影响，证明ACSL4抑制剂罗格列酮对肝癌的靶向治疗作用。本研究将揭示脂代谢重编程与周期调控交互作用促进肝癌细胞快速增殖的新机制，为临床肝癌的转化治疗提供新思路。

Metabolic reprogramming and cell cycle regulation are two hallmarks of cancer. Their interactions and the resulting promotion on cancer cell proliferation and carcinogenesis are not well understood yet. Our previous work has identified through hepatocellular carcinoma (HCC) transcriptome profiling that long chain acyl coenzyme A synthase 4 (ACSL4), an upregulated lipid metabolic reprogramming enzyme, was highly expressed in HCC and closely related to poor prognosis. ACSL4 activated c-Myc to promote G1/S phase transition in cancer cells, but the molecular mechanism remains unclear. This study aims to examine the expression patterns of ACSL4/c-Myc in HCC cells and analyze the correlation of the abnormal expressions with clinico-pathological characteristics and recurrence of HCC, as well as the prognosis of the patients. We also plan to determine the effects of ACSL4 expression on HCC cell proliferation and demonstrate the molecular mechanisms of ACSL4 regulation on c-Myc stability via FBW7, using methods such as bioinformatics, co-immunoprecipitatation, ubiquitylation, and truncation mutant assay. In addition, in vivo models such as nude mice model, tail vein injection model, and PDX model are utilized to investigate into the ability of tumorigenesis and metastasis of HCC and the effects of rosiglitazone, an ACSL4 inhibitor, on targeted therapies for HCC. This study may discover a novel mechanism of interactions between lipid metabolism reprogramming and cycle regulation on promoting cancer cell proliferation, and provide new approaches for clinical management of HCC.