ArticlePloS one2013
miR-126&126* restored expressions play a tumor suppressor role by directly regulating ADAM9 and MMP7 in melanoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
- Aptamer-guided delivery of miR-126 suppresses glioblastoma stem-like cell invasion and tumor progression.Molecular therapy. Nucleic acids · 2026Article
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- Targeting the microbiota-miRNA-protease axis: A new therapeutic avenue in melanoma.The FEBS journal · 2026Review
- Non-coding RNAs in BRAF-mutant melanoma: targets, indicators, and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Heparin-binding EGF-like growth factor via miR-126 controls tumor formation/growth and the proteolytic niche in murine models of colorectal and colitis-associated cancers.Cell death & disease · 2024Article
- Review
- MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- A New Approach to Melanoma Treatment: microRNAs.Current topics in medicinal chemistry · 2024Review
- Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors.Cancer gene therapy · 2023Article
- MitomiRs: their roles in mitochondria and importance in cancer cell metabolism.Radiology and oncology · 2021Review
- Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling.International journal of molecular sciences · 2021Article
- Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research.Cells · 2021Review
- Identification of a Competing Endogenous RNA Network Related to Immune Signature in Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets.Frontiers in oncology · 2021Review
- Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma.BioMed research international · 2021Article
- Long non-coding RNA PRNCR1 modulates non-small cell lung cancer cell proliferation, apoptosis, migration, invasion, and EMT through PRNCR1/miR-126-5p/MTDH axis.Bioscience reports · 2020Article
- MicroRNA heterogeneity in melanoma progression.Seminars in cancer biology · 2019Review
- Joint action of miR-126 and MAPK/PI3K inhibitors against metastatic melanoma.Molecular oncology · 2019Article
- miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A.Journal of experimental & clinical cancer research : CR · 2019Article
- SOX9 is a dose-dependent metastatic fate determinant in melanoma.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The abnormal expression of several microRNAs has a causal role in tumorigenesis with either antineoplastic or oncogenic functions. Here we demonstrated that miR-126 and miR-126* play a tumor suppressor role in human melanoma through the direct or indirect repression of several key oncogenic molecules. The expression levels of miR-126&126* were elevated in normal melanocytes and primary melanoma cell lines, whereas they markedly declined in metastatic cells. Indeed, the restored expression of miR-126&126* in two advanced melanoma cell lines was accompanied by a significant reduction of proliferation, invasion and chemotaxis in vitro as well as of growth and dissemination in vivo. In accordance, the reverse functional effects were obtained by knocking down miR-126&126* by transfecting antisense LNA oligonucleotides in melanoma cells. Looking for the effectors of these antineoplastic functions, we identified ADAM9 and MMP7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of miR-126&126*. In addition, as ADAM9 and MMP7 share a role in the proteolytic cleavage of the HB-EGF precursor, we looked for the effectiveness of this regulatory pathway in melanoma, confirming the decrease of HB-EGF activation as a consequence of miR-126&126*-dependent downmodulation of ADAM9 and MMP7. Finally, gene profile analyses showed that miR-126&126* reexpression was sufficient to inactivate other key signaling pathways involved in the oncogenic transformation, as PI3K/AKT and MAPK, and to restore melanogenesis, as indicated by KIT/MITF/TYR induction. In view of this miR-126&126* wide-ranging action, we believe that the replacement of these microRNAs might be considered a promising therapeutic approach.
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