ArticleThe Journal of biological chemistry2017
A-to-I RNA Editing Up-regulates Human Dihydrofolate Reductase in Breast Cancer.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Pooled it
- B-vitamin-associated miRNAs are enriched in pathways related to cell proliferation - insights from the general population.Nutrition & metabolism · 2026Article
- The regulatory mechanism and clinical significance of RNA editing in prostate cancer.Current urology · 2026Review
- RNA editing: an emerging frontier in cancer therapy - explorations, opportunities, and challenges.International journal of surgery (London, England) · 2026Article
- ADAR1 expression in different cancer cell lines and its change under heat shock.Journal of applied genetics · 2025Article
- Boron-containing anticancer agents: a target-centric review of structure-activity relationships and clinical pipeline.Archives of pharmacal research · 2025Review
- Article
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- Quantifying the mRNA epitranscriptome reveals epitranscriptome signatures and roles in cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Adenosine-to-inosine RNA editing in cancer: molecular mechanisms and downstream targets.Protein & cell · 2025Review
- RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.Biomarker research · 2025Review
- A-to-I RNA editing ofeLife · 2025Article
- ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via DrivingOncology research · 2025Article
- A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.CNS neuroscience & therapeutics · 2025Review
- Epitranscriptome-wide profiling identifies RNA editing events regulated by ADAR1 that are associated with DNA repair mechanisms in human TK6 cells.Frontiers in genetics · 2025Article
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Advances in A-to-I RNA editing in cancer.Molecular cancer · 2024Review
- REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers.Computational and structural biotechnology journal · 2024Article
- ADAR1 Promotes Myogenic Proliferation and Differentiation of Goat Skeletal Muscle Satellite Cells.Cells · 2024Article
- ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer.International journal of molecular sciences · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate. The present study investigated the possibility that adenosine-to-inosine RNA editing, which causes nucleotide conversion by adenosine deaminase acting on RNA (ADAR) enzymes, might modulate DHFR expression. In human breast adenocarcinoma-derived MCF-7 cells, 26 RNA editing sites were identified in the 3'-UTR of DHFR. Knockdown of ADAR1 decreased the RNA editing levels of DHFR and resulted in a decrease in the DHFR mRNA and protein levels, indicating that ADAR1 up-regulates DHFR expression. Using a computational analysis, miR-25-3p and miR-125a-3p were predicted to bind to the non-edited 3'-UTR of DHFR but not to the edited sequence. The decrease in DHFR expression by the knockdown of ADAR1 was restored by transfection of antisense oligonucleotides for these miRNAs, suggesting that RNA editing mediated up-regulation of DHFR requires the function of these miRNAs. Interestingly, we observed that the knockdown of ADAR1 decreased cell viability and increased the sensitivity of MCF-7 cells to methotrexate. ADAR1 expression levels and the RNA editing levels in the 3'-UTR of DHFR in breast cancer tissues were higher than those in adjacent normal tissues. Collectively, the present study demonstrated that ADAR1 positively regulates the expression of DHFR by editing the miR-25-3p and miR-125a-3p binding sites in the 3'-UTR of DHFR, enhancing cellular proliferation and resistance to methotrexate.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.