Related Experiment Video
Updated: Aug 9, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer
Yaguang Xi1, Go Nakajima, John C Schmitz
1Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36688, USA. xi@usouthal.edu
Background:
Thymidylate synthase (TS) is a critical target for cancer chemotherapy and is one of the most extensively studied biomarkers for fluoropyrimidine-based chemotherapy. In addition to its critical role in enzyme catalysis, TS functions as an RNA binding protein to regulate the expression of its own mRNA translation and other cellular mRNAs, such as p53, at the translational level. In this study, a comprehensive gene expression analysis at the levels of both transcriptional and post-transcriptional regulation was conducted to identify response markers using human genome array with TS-depleted human colon cancer HCT-C18 (TS-) cells and HCT-C18 (TS+) cells stably transfected with the human TS cDNA expression plasmid.
Results:
A total of 38 genes were found to be significantly affected by TS based on the expression profiles of steady state mRNA transcripts. However, based on the expression profiles of polysome associated mRNA transcripts, over 149 genes were affected by TS overexpression. This indicates that additional post-transcriptionally controlled genes can be captured with profiling polysome associated mRNA population. This unique approach provides a comprehensive overview of genes affected by TS. Additional novel post-transcriptionally regulated genes affected by 5-fluorouracil (5-FU) treatment were also discovered via similar approach.
Conclusion:
To our knowledge, this is the first time that a comprehensive gene expression profile regulated by TS and 5-FU was analyzed at the multiple steps of gene regulation. This study will provide candidate markers that can be potentially used for predicting therapeutic outcomes for fluoropyrimidine-based cancer chemotherapy.
Insights
Thymidylate synthase (TS) impacts gene expression at multiple levels. This study identified novel post-transcriptional gene targets of TS and 5-fluorouracil (5-FU), offering potential biomarkers for chemotherapy response.
Area of Science:
- Molecular biology
- Cancer research
- Genomics
Background:
- Thymidylate synthase (TS) is a key target in cancer chemotherapy and a biomarker for fluoropyrimidine drugs.
- TS acts as an RNA-binding protein, regulating mRNA translation, including its own and p53.
- Understanding TS's regulatory roles is crucial for improving cancer treatment.
Purpose of the Study:
- To conduct a comprehensive gene expression analysis of TS regulation at transcriptional and post-transcriptional levels.
- To identify novel response markers for fluoropyrimidine-based chemotherapy.
- To investigate the impact of TS depletion and overexpression on gene expression.
Main Methods:
- Utilized human genome arrays for gene expression profiling.
- Compared TS-depleted (TS-) and TS-overexpressing (TS+) colon cancer cells (HCT-C18).
- Analyzed both steady-state and polysome-associated mRNA transcripts to capture post-transcriptional regulation.
Main Results:
- TS significantly affected 38 steady-state mRNA transcripts.
- Over 149 genes were affected by TS overexpression when analyzing polysome-associated mRNA, revealing extensive post-transcriptional control.
- Identified novel post-transcriptionally regulated genes influenced by 5-fluorouracil (5-FU) treatment.
Conclusions:
- This study provides the first comprehensive gene expression profile regulated by TS and 5-FU across multiple regulatory steps.
- The identified genes represent potential candidate markers for predicting patient response to fluoropyrimidine chemotherapy.
- This research enhances understanding of TS function beyond enzyme catalysis, highlighting its role in gene regulation.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...