ArticleCell death discovery2024
MiRNA-449 family is epigenetically repressed and sensitizes to doxorubicin through ACSL4 downregulation in triple-negative breast cancer.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Multi-Omics Integration Identifies Ferroptosis-Related miRNA-mRNA Networks and Independent Prognostic miRNAs in Triple-Negative Breast Cancer.Journal of clinical practice and research · 2026Article
- Empowering women's health with miRNA-integrated nanochemical approaches: from reproductive health to cancer care.RSC advances · 2026Review
- All the Way: A Decade of SIRT1 in Breast Cancer.Biomedicines · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Evaluation of miR-27a-5p and miR-449a as potential serum biomarkers for breast cancer: a combined bioinformatics and experimental study.Molecular biology reports · 2025Article
- MiRNAs: main players of cancer drug resistance target ABC transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Alterations in the Expression of a Set of miRNAs in Endometrial Cancer and Their Correlation with Clinical Variables and the p53 Signaling Pathway.International journal of molecular sciences · 2025Article
- Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Immunohistochemical Prognostic Value of Nuclear and Cytoplasmic Silent Information Regulator 1 Protein Expression in Saudi Patients with Breast Cancer.Biomolecules · 2025Article
- MicroRNAs as key regulators of cancer drug resistance: insights and future directions in chemotherapy, targeted-therapy, radiotherapy, and immunotherapy.Cancer drug resistance (Alhambra, Calif.) · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Despite progress in breast cancer treatment, a significant portion of patients still relapse because of drug resistance. The involvement of microRNAs in cancer progression and chemotherapy response is well established. Therefore, this study aimed to elucidate the dysregulation of the microRNA-449 family (specifically, microRNA-449a, microRNA-449b-5p, and microRNA-449c-5p) and its impact on resistance to doxorubicin, a commonly used chemotherapeutic drug for the treatment of triple-negative breast cancer. We found that the microRNA-449 family is downregulated in triple-negative breast cancer and demonstrated its potential as a diagnostic biomarker. Besides, our findings indicate that the downregulation of the microRNA-449 family is mediated by the microRNAs-449/SIRT1-HDAC1 negative feedback loop. Moreover, it was found that the microRNA-449 family dysregulates the fatty acid metabolism by targeting ACSL4, which is a potential prognostic biomarker that mediates doxorubicin response through regulation of the drug extrusion pump ABCG2. Altogether, our results suggest that the microRNA-449 family might be a potential therapeutic target for the treatment of triple-negative breast cancer since it is implicated in doxorubicin response through ACSL4/ABCG2 axis regulation. Ultimately, our results also highlight the value of microRNAs-449 and ACSL4 as diagnostic and prognostic biomarkers in triple-negative breast cancer. Proposed model of miRNAs-449 downregulation in TNBC and doxorubicin response. MiRNAs-449 are downregulated in TNBC through a negative feedback loop with SIRT1 and HDAC1. Moreover, ACSL4 increases ABCG2 expression, thus diminishing the intracellular doxorubicin concentration and promoting doxorubicin resistance. MiRNAs-449 overexpression downregulates the ACSL4/ABCG2 axis and sensitizes doxorubicin-resistant cells to doxorubicin. Created with BioRender. TNBC: triple-negative breast cancer; DOX: doxorubicin; SIRT1: Sirtuin 1; HDAC1: Histone deacetylase 1; ACSL4: Acyl-CoA Synthetase Long-Chain Family Member 4; ABCG2: ATP-binding cassette superfamily G member 2.
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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.