ArticleCell communication and signaling : CCS2020
miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Non-oncologic to oncologic drug: A systematic review of drug repurposing in cancer.Cancer chemotherapy and pharmacology · 2025Pooled it
- The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy.International journal of molecular sciences · 2022Pooled it
- Global Proteomic Analysis Reveals Inflammatory Pathway Modulation Associated with miR-146a in LPS-Stimulated Macrophages.International journal of molecular sciences · 2026Article
- Targeting the microbiota-miRNA-protease axis: A new therapeutic avenue in melanoma.The FEBS journal · 2026Review
- 3'-sialyllactose inhibits the migration and invasion of LPS-induced B16F10 mouse melanoma cells through inactivation of the NF-Glycoconjugate journal · 2026Article
- Upregulation of miR-4286 and miR-146a-5p in Metastatic Melanoma, Revealed by Multiplex Expression Analysis.Current issues in molecular biology · 2026Article
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Pharmacological evaluation of 1-acetyl-β-carboline, a naturally occurring compound with anti-skin cancer potential.Molecular therapy. Oncology · 2025Article
- Article
- Relationship between specific microRNA expression and radioresistant conditions in HL60 acute myeloid leukemia cells.Molecular medicine reports · 2025Article
- Omics in Cutaneous Melanoma.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Old drugs, new challenges: reassigning drugs for cancer therapies.Cellular & molecular biology letters · 2025Review
- Exosomal CircMFN2 Enhances the Progression of Pituitary Adenoma via the MiR-146a-3p/TRAF6/NF-κB Pathway.Journal of neurological surgery. Part A, Central European neurosurgery · 2025Article
- Oxidative State in Cutaneous Melanoma Progression: A Question of Balance.Antioxidants (Basel, Switzerland) · 2024Review
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Astrocytic Extracellular Vesicles Regulated by Microglial Inflammatory Responses Improve Stroke Recovery.Molecular neurobiology · 2024Article
- Analysis of MicroRNA-Transcription Factors Co-Regulatory Network Linking Depression and Vitamin D Deficiency.International journal of molecular sciences · 2024Article
- Exploring resistance to immune checkpoint inhibitors and targeted therapies in melanoma.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- BRAF V600-Mutated Metastatic Melanoma and Targeted Therapy Resistance: An Update of the Current Knowledge.Cancers · 2023Review
- Molecular inhibition of RAS signalling to target ageing and age-related health.Disease models & mechanisms · 2022Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance.
methodsThe miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy.
resultsmiR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor.
conclusionsDeregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract.
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