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MicroRNAs and melanoma

European scientists have investigated how the microenvironment drives melanoma metastasis independently of mutation. Their results have important therapeutic significance.
MicroRNAs and melanoma
Melanoma is a highly lethal and treatment-refractory cancer that develops in the melanin-producing cells of the skin. Although considerable knowledge has been gained over the years on the molecular causes of melanoma, treatment of metastatic disease is poor.

The EU-funded MICRORNA & MELANOMA (Dissecting intracellular signalling of melanoma invasion towards microRNA-based therapy) worked under the hypothesis that complex cellular phenotype changes – such as the cancer cell phenotype – involve many genes and cannot be regulated in a single step. MicroRNAs are small non-coding RNA molecules known for their capacity to regulate gene expression. In essence, a single microRNA could target thousands of genes and hence regulate complex phenotypes. In this context, researchers had identified the melanoma-specific miR-211that displayed a tumour suppressive function and negatively regulated melanoma invasiveness.

During MICRORNA & MELANOMA, they studied how microRNAs could be implicated in the interplay between the microenvironment and the radial to vertical growth transition, the most critical stage in initiation of melanoma metastasis. Results showed that direct contact of melanoma cells with the remote epidermal layer triggered vertical invasion. This occurred through activation of Notch signalling and binding inhibition of the melanocyte lineage master regulator (MITF) to the miR-222/221 promoter. Unlike miR-211, miR-222/221 was identified to have a promoting role on initiating melanoma invasion.

Taken together, the findings of the study underscore the role of microRNAs in promotion or suppression of tumour growth and invasion. In melanoma, these observations could lead to new opportunities for preventing melanoma metastasis by targeting specific microenvironments.

Related information

Keywords

microRNA, melanoma, microenvironment, metastasis, Notch, MITF, miR222/221
Record Number: 188742 / Last updated on: 2016-10-26
Domain: Biology, Medicine
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