ArticlePloS one2015
MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Pooled it
- MicroRNAs and Alarmins in Cardio-Oncology: Biomarkers and Therapeutic Implications in Skin and Breast Cancer.International journal of molecular sciences · 2026Review
- Review
- Targeting the microbiota-miRNA-protease axis: A new therapeutic avenue in melanoma.The FEBS journal · 2026Review
- The role of non-coding RNAs in the regulation of cell death pathways in melanoma.Discover oncology · 2025Review
- Integration of MicroRNAs with nanomedicine: tumor targeting and therapeutic approaches.Frontiers in cell and developmental biology · 2025Review
- Evaluation of Clinically Significant miRNAs Level by Machine Learning Approaches Utilizing Total Transcriptome Data.Doklady. Biochemistry and biophysics · 2024Article
- Determination of Common microRNA Biomarker Candidates in Stage IV Melanoma Patients and a Human Melanoma Cell Line: A Potential Anti-Melanoma Agent Screening Model.International journal of molecular sciences · 2023Article
- Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer.Journal of translational medicine · 2023Article
- RETRACTED: Expression of microRNAs and their target genes in melanomas originating from gynecologic sites.PloS one · 2023Article
- Transcriptomic landscape of TIMP3 oncosuppressor activity in thyroid carcinoma.Cancer cell international · 2022Article
- Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis.Journal for immunotherapy of cancer · 2022Article
- Non-coding RNAs in skin cancers:Biological roles and molecular mechanisms.Frontiers in pharmacology · 2022Review
- Article
- Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression.Cells · 2021Review
- Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps.International journal of molecular medicine · 2021Article
- MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis.International journal of molecular sciences · 2021Review
- MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets.Frontiers in oncology · 2021Review
- MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis.International journal of general medicine · 2021Article
- MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies.International journal of molecular sciences · 2020Review
1 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
12 authors at 5 institutions in 1 country.
Funding
Abstract
Metastatic melanoma is the most aggressive form of this cancer. It is important to understand factors that increase or decrease metastatic activity in order to more effectively research and implement treatments for melanoma. Increased cell invasion through the extracellular matrix is required for metastasis and is enhanced by matrix metalloproteinases (MMPs). Tissue inhibitor of metalloproteinases 3 (TIMP3) inhibits MMP activity. It was previously shown by our group that miR-21, a potential regulator of TIMP3, is over-expressed in cutaneous melanoma. It was therefore hypothesized that increased levels of miR-21 expression would lead to decreased expression of TIMP3 and thereby enhance the invasiveness of melanoma cells. miR-21 over-expression in the melanoma cell lines WM1552c, WM793b, A375 and MEL 39 was accomplished via transfection with pre-miR-21. Immunoblot analysis of miR-21-overexpressing cell lines revealed reduced expression of TIMP3 as compared to controls. This in turn led to a significant increase in the invasiveness of the radial growth phase cell line WM1552c and the vertical growth phase cell line WM793b (p < 0.05), but not in the metastatic cell lines A375 or MEL 39. The proliferation and migration of miR-21 over-expressing cell lines was not affected. Reduced expression of TIMP3 was achieved by siRNA knockdown and significantly enhanced invasion of melanoma cell lines, mimicking the effects of miR-21 over-expression. Treatment of tumor cells with a linked nucleic acid antagomir to miR-21 inhibited tumor growth and increased tumor expression of TIMP3 in vivo in 01B74 Athymic NCr-nu/nu mice. Intra-tumoral injections of anti-miR-21 produced similar effects. This data shows that increased expression of miR-21 enhanced the invasive potential of melanoma cell lines through TIMP3 inhibition. Therefore, inhibition of miR-21 in melanoma may reduce melanoma invasiveness.
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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.