ENAGenomicsInstitute for Advanced Biosciences, Keio Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA350248Mus musculusxref:PubMed:28847964Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here, we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multi-omics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS and CTPS blocked cell growth, and thus they are potential targets for colorectal cancer therapy. Overall design: Gene expression in normal and adenomatous tissue obtained from the large intestines of Apc+/Δ716 miceENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscaris3.4.22.-, D-APC1, D-APC2, D-Axin, e-apc, Laboratory, Daxin, Mus domesticus, Gene, DNA Microchips, DNA Arrays, apc, mini-ICE, axn, CASP-14, House Mouse, DP3, PPP1R46, DP2, d-axin, House, DAPC, CG6193, Mus musculus domesticus, Min, BTPS2, GSK3beta, DNA Chip, CG1451, D-APC, Mice, cDNA Microarray, Arrays, Microchip, dApc, dAPC, portion of tissue, Oligonucleotide Microarrays, cDNA Microarrays, Chip, Swiss, Tissue, Microchips, mAPC, Swiss Mice, CG7926, AI047805, cDNA Arrays, dAPC2/E-APC, Chips, cyclosome, Oligonucleotide Microarray, Oligonucleotide Arrays, DNA Array, DmelCG6193, dAxin, DmelCG1451, dApc2, din, l(3)S044230, Microarray, Gene Chip, E-APC, DP2.5, mouse, DNA-array, cDNA, Oligonucleotide, d-APC, APC2, dAXIN, Apc1, Oligonucleotide Array, APC1, DNA Chips, xapc, Microarrays, E-APC dAPC2, Mus, Gene Chips, apc 1, Mini-ICE, apc1, tissue portion, axin, apc2, simple tissue, d-APC2, Mus musculus., dAPC2, DNA Microarray, dAPC1, AU020952, Mus musculus, cDNA Array, Caspase-14 subunit p10, mice, CC1, 0442/30, Swiss Mouse, House Mice, Caspase-14 subunit p19, AW124434, MICE, Dm APC2, Dm APC1, DAxin, Laboratory Mice, domesticus, DNA Microarrays, Gene Expression Microarray Analysis, GS, DmelCG7926, Array, APC, Mouse, DNA, anaphase promoting complex, Oligodeoxyribonucleotide Array Sequence Analysis, Sequence Analysis, Laboratory Mouse, DNA MicrochipfalseMus musculusDNA microarray analysis of colorectal tissue from Apc mutant mice2025-09-242017-09-10PRJNA350248GSE890771009028847964