ArticleBMC cancer2014
Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 4 of them syntheses that pooled it.
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Who cites it
69 citing papers in PubMed, 4 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Circulating and Tissue MicroRNA Profiles Associated with Pathological Complete Response in HER2+ Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Pooled it
- Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis.BioMed research international · 2017Pooled it
- Prognostic significance of microRNA-375 downregulation in solid tumors: a meta-analysis.Disease markers · 2014Pooled it
- IGF1R Protein Expression Is Not Associated with Differential Benefit to Concurrent Trastuzumab in Early-Stage HER2Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Integrated roles of miR-125b, miR-375, and miR-451 in breast cancer chemoresistance: mechanistic insights and translational implications.Molecular biology reports · 2026Review
- MicroRNA-Directed Biomarkers and Breast Cancer Therapeutics-Potential to Advance Personalised Approaches in Clinical Trials.International journal of molecular sciences · 2026Review
- Review
- Integrated miRNA-mRNA Analyses of Triple-Negative Breast Cancer in Black and White Patients with or Without Obesity.International journal of molecular sciences · 2025Article
- The mechanism of ncRNA in trastuzumab resistance in HER2-positive tumors.Medical oncology (Northwood, London, England) · 2025Review
- Targeting drug resistance in breast cancer: the potential of miRNA and nanotechnology-driven delivery systems.Nanoscale advances · 2024Review
- A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bergenin protects against osteoarthritis by inhibiting STAT3, NF-κB and Jun pathways and suppressing osteoclastogenesis.Scientific reports · 2024Article
- miRNAs as biomarkers of therapeutic response to HER2-targeted treatment in breast cancer: A systematic review.Biochemistry and biophysics reports · 2024Review
- Advances in understanding the role and mechanisms of tumor stem cells in HER2-positive breast cancer treatment resistance (Review).International journal of oncology · 2023Review
- Cancer-derived exosomal miR-375 targets DIP2C and promotes osteoblastic metastasis and prostate cancer progression by regulating the Wnt signaling pathway.Cancer gene therapy · 2023Article
- Breast cancer: miRNAs monitoring chemoresistance and systemic therapy.Frontiers in oncology · 2023Review
- Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications.International journal of molecular sciences · 2022Review
- LINC00589-dominated ceRNA networks regulate multiple chemoresistance and cancer stem cell-like properties in HER2NPJ breast cancer · 2022Article
- The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy.Medicina (Kaunas, Lithuania) · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to humanized monoclonal erbB2/HER2 antibody, trastuzumab (Herceptin), has become a pivotal obstacle for targeted therapy of HER2-positive breast cancers. The activation of alternative growth factor receptors, in particular, the insulin-like growth factor 1 receptor (IGF1R), represents a common feature of trastuzumab-refractory cells; however, the underlying mechanism remains elusive.
methodsTrastuzumab-resistant breast cancer SKBr-3 cells were generated by long-term in vitro culture of SKBr-3 cells in the presence of trastuzumab. Among the differentially expressed microRNAs (miRNAs) screened by microarray analysis, candidate miRNA(s) predicted to target IGF1R was studied for its role in conferring trastuzumab resistance. The mechanism underlying decreased expression of IGF1R-targeted miRNA in refractory cells was also addressed.
resultsmiR-375, which was downregulated and predicted to target IGF1R in trastuzumab-resistant HER2-positive breast cancer cells, could indeed inhibit the cellular luciferase activity in a reporter construct containing the 3'-UTR of IGF1R. Overexpression of miR-375 restored the sensitivity of cells to trastuzumab, while inhibition of miR-375 conferred trastuzumab resistance on HER2-positive breast cancer cells. Blockade of DNA methylation and histone deacetylation restored the expression of miR-375 in trastuzumab-resistant cells. A reverse correlation between the levels of miR-375 and IGF1R was validated in clinical breast cancers.
conclusionsEpigenetic silencing of miR-375 causes the upregulation of IGF1R, which at least partially underlies trastuzumab resistance of breast cancer cells. Our study has implications for miR-375 as a potential target in combination with trastuzumab for treating HER2-positive breast cancers.
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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.