Abstract：
Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1\'s established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.
摘要：
代谢重编程被认为是癌症的标志，使癌细胞获得细胞生长所必需的生物分子，通常以上调的糖酵解和/或脂肪酸合成相关基因为特征。转录因子叉头框M1（FOXM1）与各种癌症有关，对他们的发展做出重大贡献，包括结直肠癌（CRC），一个重大的全球健康问题。尽管FOXM1在癌症中的作用已经确立，其在CRC的Warburg效应和脂肪酸生物合成中的具体参与尚不清楚.我们分析了癌症基因组图谱（TCGA）结肠腺癌和直肠腺癌（COADREAD）数据集，以得出FOXM1和多个基因之间的表达水平与基于FOXM1表达的生存预后的相关性。使用两种人类CRC细胞系，HT29和HCT116，我们进行了RNAi或质粒转染程序，接着是一系列的化验,包括RNA提取，定量实时聚合酶链反应，蛋白质印迹分析,细胞代谢测定，和免疫荧光分析。较高的FOXM1表达水平与较差的生存预后相关。FOXM1的表达与糖酵解相关基因SLC2A1和LDHA呈正相关,从头脂肪生成相关基因ACACA和FASN，MYCFOXM1似乎调节AKT/mTOR信号，c-Myc的表达，与糖酵解和脂肪酸生物合成有关的蛋白质，以及HT29和HCT116细胞的细胞外酸化率。总之,FOXM1在糖酵解中起调节作用，脂肪酸生物合成，和细胞能量消耗，从而影响CRC细胞生长和患者预后。
