Article
High-fat diet driven post-operative colon cancer recurrence is dependent upon genetic susceptibility to deoxycholic acid
Published in
Cancer Letters
Abstract
Dietary factors that determine whether colorectal cancer returns after surgery are poorly defined. Using a mouse model of postoperative tumor formation, the authors show that a high-fat diet accelerates recurrence only when the primary tumor carries certain genetic lesions, particularly APC mutations. Deoxycholic acid (DCA), a secondary bile acid that rises during high-fat feeding, emerged as the key mediator. Combining transcriptomic and tRNA-focused analyses, the team found that DCA reshapes tRNA abundance, modification, and charging, which in turn sharpens codon-biased translation of proliferation-associated genes. The work draws a direct line from diet through tRNA regulation to colorectal cancer recurrence.
Results
• A high-fat diet strongly promotes postoperative colorectal cancer recurrence, but only in a genotype-dependent manner.
• The tumor-promoting effect is greatest in tumors driven by APC mutations.
• DCA, a high-fat-diet-associated secondary bile acid, is a major driver of recurrence.
• DCA stimulates proliferation of colorectal cancer organoids from APC-mutant tumors.
• DCA alters tRNA abundance, modification patterns, and charging status, profiled by multiplex small RNA sequencing (MSR-seq).
• Integrated mRNA and tRNA sequencing reveal enhanced decoding of codons enriched in proliferation-promoting genes.
• tRNA pool reprogramming favors translational output that sustains tumor growth and recurrence after resection.
Fig. 1. High-fat-diet-derived deoxycholic acid reprograms tRNA abundance, modification, and charging to drive codon-biased translation of proliferation-associated genes and postoperative colorectal cancer recurrence.
Conclusion
This study demonstrates that diet can influence postoperative colorectal cancer recurrence through the tRNA translation machinery. DCA produced by high-fat feeding alters tRNA abundance, modification, and charging, improving the decoding of codons within proliferation-promoting transcripts. tRNA charging and codon-biased translation thus emerge as critical bridges between diet, tumor genetics, and recurrence, and they point toward new opportunities for therapeutic intervention.
tRNA Charging Sequencing
Arraystar tRNA Charging Seq (modification-induced misincorporation tRNA-seq) delivers simultaneous tRNA expression, modification, and charging profiles in a single experiment. The service supports tRNA studies in cancer drug resistance, cardiac fibrosis, and many other disease areas.
Advantages
• One assay, three profiles: tRNA expression, tRNA modification, and tRNA charging.
• Full-length tRNA enrichment: high-efficiency full-length cDNA synthesis reduces mapping and counting inaccuracy.
• Broad modification coverage: m1A, m1G, m3C, acp3U and more predicted at single-nucleotide resolution.
• Translatomics-ready: correlates tRNA charging with translational activity.
• Rich outputs: multi-omics data with differential analyses and detailed annotations.
• Publication-ready graphics and visualization.