In contast with those of healthy women, microRNAs in the melanocytes of women with a history of melanoma were “dramatically” down-regulated when exposed to ultraviolet radiation.1
The results of a recent study strongly indicate that, when exposed to simulated UV radiation, down-regulation in UV-sensitive microRNAs causes the melanocytes of women with a history of melanoma to control epithelial-to-mesenchymal (EMT) transition. Melanocytes in women with no history of cancer, in contrast, switch to a protective mode when exposed to UV radiation.
“The types of mRNAs that were altered in expression allowed us to predict the types of proteins and molecular pathways that were altered in these seemingly normal skin cells,” said Brian Gastman, MD, plastic surgeon and director of melanoma at the Cleveland Clinic in Ohio. “By identifying these mechanisms, inhibitory strategies can be designed, and perhaps melanoma will be a preventable disease regardless of a patient’s sun exposure history.”
For the study, a team of researchers recruited 17 fair-skinned women aged 31 to 46. Nine participants had 1 previous primary melanoma; the other 8 had no history of skin cancer.
The lowest dose of irradiation at which each woman’s skin would develop sunburn was established, and a small patch of each participant’s skin was exposed to a dose of simulated UV radiation equivalent to approximately 3 hours of midday sun. The same patch of skin was irradiated again 24 hours later.
Skin biopsies of the irradiated site and an adjacent non-exposed site were taken 24 hours after the second exposure.
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Using laser capture microdissection (LCM) to isolate a pure population of melanocytes, researchers found that an average of 122 of 667 microRNAs in healthy women were deregulated, most of which were up-regulated. In contrast, women with a history of skin cancer had an average of 133 deregulated microRNAs, the vast majority of which were down-regulated in expression.
Dr Gastman called the differences in expression between the 2 groups “drastic.”