ArticleThe pharmacogenomics journal2013
Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.
Article in The pharmacogenomics journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type.Frontiers in immunology · 2025Review
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
- Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.World journal of gastroenterology · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
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- Construction of a nine DNA repair-related gene prognostic classifier to predict prognosis in patients with endometrial carcinoma.BMC cancer · 2021Article
- The Mysteries around the BCL-2 Family Member BOK.Biomolecules · 2020Review
- Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population.Communications biology · 2020Article
- Article
- 5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes.Cancer science · 2020Review
- Identification of COVID-19 Infection-Related Human Genes Based on a Random Walk Model in a Virus-Human Protein Interaction Network.BioMed research international · 2020Article
- Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Endometrial Cancer.Frontiers in genetics · 2020Article
- BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
- Pathway analysis of genetic variants in folate-mediated one-carbon metabolism-related genes and survival in a prospectively followed cohort of colorectal cancer patients.Cancer medicine · 2018Article
- Recent studies of 5-fluorouracil resistance in pancreatic cancer.World journal of gastroenterology · 2014Review
- A pan-cancer analysis of alternative splicing events reveals novel tumor-associated splice variants of matriptase.Cancer informatics · 2014Article
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Authors and funding
27 authors at 4 institutions in 1 country.
Funding
Abstract
The drug fluorouracil (5-FU) is a widely used antimetabolite chemotherapy in the treatment of colorectal cancer. The gene uridine monophosphate synthetase (UMPS) is thought to be primarily responsible for conversion of 5-FU to active anticancer metabolites in tumor cells. Mutation or aberrant expression of UMPS may contribute to 5-FU resistance during treatment. We undertook a characterization of UMPS mRNA isoform expression and sequence variation in 5-FU-resistant cell lines and drug-naive or -exposed primary and metastatic tumors. We observed reciprocal differential expression of two UMPS isoforms in a colorectal cancer cell line with acquired 5-FU resistance relative to the 5-FU-sensitive cell line from which it was derived. A novel isoform arising as a consequence of exon skipping was increased in abundance in resistant cells. The underlying mechanism responsible for this shift in isoform expression was determined to be a heterozygous splice site mutation acquired in the resistant cell line. We developed sequencing and expression assays to specifically detect alternative UMPS isoforms and used these to determine that UMPS was recurrently disrupted by mutations and aberrant splicing in additional 5-FU-resistant colorectal cancer cell lines and colorectal tumors. The observed mutations, aberrant splicing and downregulation of UMPS represent novel mechanisms for acquired 5-FU resistance in colorectal cancer.
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