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NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis
Date:2/9/2009

messenger RNAs. They serve as regulators of protein expression, acting like the volume control on a radio. In recent years, miRNAs have been linked to the over- or under-expression of a variety of genes linked to cancer and other diseases.

Dr. Hernando's lab found a miRNA is over-expressed in metastatic melanoma cell lines and tissues. The lab found that the elevated expression of miRNA 182 turns it into an oncogene (a gene involved in cancer tumor initiation or progression), by increasing the invasive capacity of melanoma cells in vitro and stimulating the cell's metastatic potential in a mouse model.

In addition, the NYU scientists found that miRNA 182 also represses the expression of two tumor suppressors called FOXO3 and MITF, which normally prevent cells from becoming malignant. By repressing the suppressors, miRNA 182 permits melanoma cells to migrate and survive independently, two properties necessary for metastasis.

MiRNA 182 also belongs to a cluster located in a genomic region, chromosome 7q, that is frequently amplified in melanoma and contains two other oncogenes; BRAF and C-MET. The study found a correlation between genomic amplification and miRNA over expression, though it is unclear whether other molecular mechanisms play a role in this effect, according to Dr. Hernando.

Finally, the scientists observed that in a significant fraction of metastatic melanomas, high miRNA 182 levels correlate with low levels of FOXO3 and MITF, supporting the relevance of this mechanism in human melanoma.

The study suggests that miRNA 182 is a novel therapeutic target. When it is inhibited, it impairs the invasive potential of melanoma cells and induces cell death. In theory, the administration of anti-miRNA 182 could block the growth or expansion of the primary melanoma tumor. Several academic laboratories and pharmaceutical companies are working to improve the delivery o
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Contact: Nadine Woloshin
nwoloshin@rubenstein.com
212-843-8041
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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