ArticleBMC cancer2013
MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- A Systematic Review of Clinical Validated and Potential miRNA Markers Related to the Efficacy of Fluoropyrimidine Drugs.Disease markers · 2022Pooled it
- Recent advances in novel targeting mechanisms for colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Unveiling the oncogenic significance of thymidylate synthase in human cancers.American journal of translational research · 2024Article
- The Critical Function of microRNAs in Developing Resistance against 5- Fluorouracil in Cancer Cells.Mini reviews in medicinal chemistry · 2024Review
- Metabolomics in oncology.Cancer reports (Hoboken, N.J.) · 2023Review
- Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.Cell communication and signaling : CCS · 2023Review
- MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.Brain and behavior · 2022Article
- MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.Virchows Archiv : an international journal of pathology · 2022Article
- Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells.Metabolites · 2022Article
- Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.Cells · 2021Review
- LncRNA HOTAIRM1, miR-433-5p and PIK3CD function as a ceRNA network to exacerbate the development of PCOS.Journal of ovarian research · 2021Article
- All-Trans Retinoic Acid Enhances Chemosensitivity to 5-FU by Targeting miR-378c/E2F7 Axis in Colorectal Cancer.Journal of oncology · 2021Article
- Anti-Tumor Effect of Apatinib and Relevant Mechanisms in Liposarcoma.Frontiers in oncology · 2021Article
- 5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent.Frontiers in oncology · 2021Review
- Expression of miR-129-5p and miR-433 in the serum of breast cancer patients and their relationship with clinicopathological features.Oncology letters · 2020Article
- MicroRNA-375-3p enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer.Cancer science · 2020Article
- miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance.MicroRNA (Shariqah, United Arab Emirates) · 2020Review
- Article
- Melatonin-mediated downregulation of thymidylate synthase as a novel mechanism for overcoming 5-fluorouracil associated chemoresistance in colorectal cancer cells.Carcinogenesis · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThymidylate synthase (TYMS) is an important folate-dependent enzyme in DNA synthesis and an important target for cancer chemotherapy. High TYMS expression levels in tumors are generally associated with resistance to 5-fluorouracil (5-FU). The cause of the variability in TYMS expression is still not fully understood, however, only a small proportion of the TYMS expression can be explained by TYMS genetic polymorphisms. The purpose of this study is to identify novel microRNAs (miRNAs) which regulate the expression of TYMS and to determine whether miRNAs binding to the 3'-untranslated region (UTR) of TYMS mRNA affect the proliferation of HeLa cells treated with 5-FU.
methodsAn in silico search was performed to find potential binding sites of miRNAs in TYMS mRNA. The efficacy of predicted miRNAs at the 3'-UTR of TYMS mRNA was evaluated using a dual-luciferase reporter assay. TYMS mRNA and protein expression in HeLa cells was quantified with real-time RT-PCR and Western blotting, respectively. The effects of miR-433 on cell proliferative activity were determined by WST-8 assay.
resultsThe overexpression of miR-433 was associated with significantly decreased reporter activity in the plasmid containing the 3'-UTR of TYMS mRNA (P < 0.01). The levels of TYMS mRNA and protein in HeLa cells were significantly decreased by the overexpression of miR-433 (P < 0.05). Furthermore, miR-433 increased inhibition of cell proliferation in HeLa cells treated with 5-FU at over 2.0 μM.
conclusionThe results indicate that miR-433 post-transcriptionally regulates the expression of TYMS mRNA and protein, and increases sensitivity to 5-FU in HeLa cells. This is the first report showing that a miRNA regulating TYMS expression has a significant impact on sensitivity to 5-FU treatment.
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