ArticleThe Journal of biological chemistry2008
MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05814224 (Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA), which is not on this map. Cited by 425 papers, 3 of them syntheses 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.
Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Who cites it
425 citing papers in PubMed, 3 syntheses or guidelines pooled it, 742 citations in OpenAlex.
- Hormone, Targeted, and Combinational Therapies for Breast Cancers: From Humans to Dogs.International journal of molecular sciences · 2024Pooled it
- miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools.Biomedical engineering online · 2021Pooled it
- Pooled it
- Dark matter matters: from noncoding RNA regulation to cancer immunity.Oncoimmunology · 2026Review
- Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy.Advanced healthcare materials · 2026Article
- CDKN1B inactivation impacts ER signaling and drives resistance to endocrine therapy in breast cancer.British journal of cancer · 2026Article
- State-Aware RNA Biomarkers in Triple-Negative Breast Cancer (TNBC): Integrating Tumor Plasticity, Spatial Architecture, and Temporal Monitoring.International journal of molecular sciences · 2026Review
- miR-548as-5p promotes breast cancer cell apoptosis and improves tamoxifen resistance by downregulating NF-κB1.Molecular biology reports · 2026Article
- Exosomal MicroRNAs as Drivers of Desmoplasia and Treatment Resistance in Breast Cancer: Mechanisms, Biomarker Potential, and Therapeutic Opportunities.Biomolecules · 2026Review
- MicroRNA-Directed Biomarkers and Breast Cancer Therapeutics-Potential to Advance Personalised Approaches in Clinical Trials.International journal of molecular sciences · 2026Review
- Non-coding RNA-mediated mechanisms underlying tamoxifen resistance in breast cancer.Discover oncology · 2026Review
- Circulating MicroRNA in Breast Cancer.Cancers · 2026Review
- microRNA involvement in human cancer.Carcinogenesis · 2025Review
- Emerging strategies for targeting vasculogenic mimicry in breast cancer treatment.Discover oncology · 2025Review
- Exploring the role of miR-221/222 in gastrointestinal cancers: implications for innovative therapeutic strategies.Cancer cell international · 2025Review
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Genetic and epigenetic contribution to tamoxifen resistance in breast cancer, concepts to drive therapeutic strategies.Discover oncology · 2025Review
- Diagnostic accuracy of circulating miR-146, miR-221 and miR-222 in papillary thyroid cancer: A systematic review and meta-analysis.World journal of clinical cases · 2025Article
- Invasive lobular carcinoma: integrated multi-omics analysis reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance.Cell death & disease · 2025Article
- Therapeutic Applications of Poly-miRNAs and miRNA Sponges.International journal of molecular sciences · 2025Review
365 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
8 authors at 1 institution in 1 country.
Funding
Abstract
We explored the role of microRNAs (miRNAs) in acquiring resistance to tamoxifen, a drug successfully used to treat women with estrogen receptor-positive breast cancer. miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHT(R))) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHT(R) cells compared with parental MCF-7 cells. Increased expression of three of the most promising up-regulated (miR-221, miR-222, and miR-181) and down-regulated (miR-21, miR-342, and miR-489) miRNAs was validated by real-time reverse transcription-PCR. The expression of miR-221 and miR-222 was also significantly (2-fold) elevated in HER2/neu-positive primary human breast cancer tissues that are known to be resistant to endocrine therapy compared with HER2/neu-negative tissue samples. Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27(Kip1), a known target of miR-221/222, was reduced by 50% in OHT(R) cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27(Kip1) in the resistant OHT(R) cells caused enhanced cell death when exposed to tamoxifen. This is the first study demonstrating a relationship between miR-221/222 expression and HER2/neu overexpression in primary breast tumors that are generally resistant to tamoxifen therapy. This finding also provides the rationale for the application of altered expression of specific miRNAs as a predictive tamoxifen-resistant breast cancer marker.
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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.