Researchers at NYU Langone Medical Center and NYU Langone’s Laura and Isaac Perlmutter Cancer Center recently reported their findings on two molecules of non-coding genetic material that are able to stall the spread of melanoma. The study, entitled “Identification of Metastasis-Suppressive microRNAs in Primary Melanoma,” which was published in the Journal of the National Cancer Institute, represents the largest epigenetic analysis so far focusing on cell-signaling molecules in early-stage melanoma.
Melanoma is the most dangerous form of skin cancer and is caused by damage to skin cells (usually by ultraviolet radiation from sunshine or tanning beds), triggering mutations that are not repaired and allowing skin cells to rapidly multiply and generate malignant tumors. Melanoma is curable when detected and treated early; if it goes undetected or if it recurs, the cancer can proliferate and spread to other parts of the body, becoming more difficult to treat. This is why it is important to have a better understanding of the molecular mechanisms behind differential tumor progression and spread.
MicroRNAs correspond to a class of non-coding RNAs (i.e. not translated into proteins) that exert key roles in the regulation of gene expression. Researchers analyzed microRNA dysregulation in primary melanoma tissue samples from 92 patients present at the NYU Langone research database. Of these patients, 48 had aggressive forms of cancer. Several techniques were applied in order to determine which miRNAs, if any, potentially regulated metastasis formation and cancer spread.
Researchers identified two microRNAs – miR-382 and miR-516b – which exhibited a lower expression in aggressive metastatic primary tumors in comparison with localized nonaggressive tumors that did not spread. These two miRNAs were found to suppress in vitro invasion and the formation of metastasis in vivo, stalling cancer spread. In particular, miR-382 was found to directly target actin regulators (namely, CTTN, RAC1, and ARPC2) resulting in the inhibition of extracellular matrix degradation by melanoma cells. Experiments were also performed in rodent models, where suppression of cancer spread was observed in mice injected with human melanoma cells engineered to over-activate either one of the two miRNAs found.
“Our study results show the suppressive effects of two specific microRNAs in melanoma that are less active in aggressive, primary tumors,” said the study’s senior author Dr. Eva Hernando in a news release. “Going forward, our goal is to show how we can use this information to identify patients more at risk of aggressive disease, and see whether early, more intense therapy improves survival from melanoma,”
According to Dr. Iman Osman, one of the study’s authors, “Now that we know that the fate of these melanoma tumors is set and predetermined by these microRNAs, we can investigate whether the same principle applies in other tumors and what interventions are possible to prevent or stall their predestined spread.”
The researchers believe that these micro RNAs can be used in future clinical tests to identify melanomas that are more likely to spread and become fatal. As such, a follow-up clinical study has already began, focusing on the possibility that microRNA(s) with an identical similar prognostic value could be able to identify melanoma patients whose cancer has a higher probability of spreading into the brain. This is quite relevant, as according to the team, almost half of the patients who succumb to melanoma actually die from brain metastasis.
