A series of aerobic glycolysis-related assays indicated that fasting plays a vital role in inhibiting glycolysis in CRC cells. the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis. signaling15C18. Although fasting exerts extensive antitumor effects in numerous contexts, the impact of fasting on metabolic changes in CRC remains poorly studied. Aberrant metabolism has been considered a hallmark of cancer cells, and this important research field has recently attracted interest19,20. Unlike normal cells, which derive most of their energy from mitochondrial oxidative phosphorylation, cancer cells rely on aerobic glycolysis as their primary energy resource. This process is recognized as the Warburg effect21C23. signaling has been suggested to play critical roles in promoting glycolysis and lactate production and thus in the metabolic reprogramming of cancer cells24C28. However, fasting could reprogram metabolic derangements to inhibit cancer growth8,29C31. Therefore, an understanding of the effects of fasting on metabolic alterations in CRC could lead to better therapeutic approaches. Farnesyl-diphosphate farnesyltransferase 1 (transcription is associated with increased invasion in prostate cancer, the exact role of in CRC progression has not been investigated35. However, our results indicated that fasting upregulated the expression of during the inhibition of CRC cell glucose metabolism and proliferation. Clinically, high expression in CRC is associated with better prognosis in The Cancer Genome Atlas (TCGA) data sets. This finding prompted us to speculate that may play a negative regulatory role in glucose metabolism, which is a critical aspect in the fasting-mediated suppression of CRC oncogenesis and progression. In this study, we provide ample evidence that fasting negatively regulates glucose metabolism and proliferation via the axis in CRC. Overall, our results indicate that is a key downstream target of the fasting response and involve in CRC cell glucose metabolism. More broadly, our present study also suggests potential therapeutic implications (involving fasting and tests. *is upregulated by fasting and correlates with prognosis Flucytosine in CRC To further explore the effect of fasting on the proliferation of CRC cells, the “type”:”entrez-geo”,”attrs”:”text”:”GSE60653″,”term_id”:”60653″GSE60653 data set28 (from a study on fasting-induced anti-Warburg effects in CRC) was analyzed to identify DEGs between the control and fasting groups (Supplementary Figs.?8a, b and Flucytosine 9a, b). Gene Ontology and KEGG pathway analyses for the DEGs were performed using FunRich software (http://www.funrich.org/). Surprisingly, the most enriched biological pathway and biological process were the Cholesterol biosynthesis pathway and the Energy pathway and Metabolism processes (Supplementary Fig.?9cCf). Via the Database for Annotation, Visualization and Integrated Discovery (DAVID, https://david.ncifcrf.gov/), the top significantly enriched biological process and KEGG pathway were the Cholesterol biosynthetic process and the Steroid biosynthesis pathway, respectively (Supplementary Fig.?10a, b). acts at the beginning of the Steroid biosynthesis pathway. Therefore, we chose the as our hub gene for further research. First, we Rabbit Polyclonal to Cytochrome P450 2U1 validated that fasting can upregulate expression. In the “type”:”entrez-geo”,”attrs”:”text”:”GSE60653″,”term_id”:”60653″GSE60653 data set, the expression of was increased significantly in the fasting group compared with that in the Flucytosine control group (Fig.?2a). Furthermore, in the iTRAQ proteomics analysis, the relative expression of was greatly elevated in the fasting group compared with that in Flucytosine the control group (Fig.?2b). In addition, the mRNA expression of in dissected tumor samples from the fasting mimic group and the control group was measured by qRT-PCR. The mRNA expression of was markedly increased in the fasting group (Fig.?2c), and western blotting indicated that fasting mimic medium increased the protein level of in cells (Fig.?2d, e). Our results thus showed that fasting upregulates the expression of in CRC. Open in a separate window Fig. 2 Fasting upregulates the level of FDFT1, which is correlated with prognosis in CRC.a The expression of was increased significantly in the fasting group compared with that in the control group in the “type”:”entrez-geo”,”attrs”:”text”:”GSE60653″,”term_id”:”60653″GSE60653 data set (was also increased greatly in the fasting group compared with that in the control group by iTRAQ (in dissected tumor tissue from.