New target could predict melanoma
A new study suggests that the majority of UV-responsive microRNAs (miRNAs) in melanocytes of women with a history of melanoma are down-regulated when compared with healthy controls’ melanocytes.
The findings, according to the study’s researchers, help to address unanswered questions about melanocytes in melanoma. That is, while it is known that the conversion of melanocytes into cutaneous melanoma is largely a result of solar ultraviolet radiation, researchers have not yet described exactly how these cells are affected by intense solar ultraviolet radiation in their natural microenvironment, as well as whether their response differs in people who have a history of melanoma versus healthy individuals, according to the study’s abstract.
The authors studied eight healthy females in their 30s, with Fitzpatrick skin type I or II. None had medical or dermatologic histories, and the women were closely matched in their exposure to sunlight over the years. The other group of participants was made up of nine females with Fitzpatrick skin types I or II, between the ages of 35 to 46 — each with a history of having one primary melanoma.
The researchers isolated a pure population of melanocytes from a small area of skin (without melanoma) that had been intermittently exposed or unexposed to solar ultraviolet radiation from each woman.
“The results were dramatic, the mRNA’s of the cancer patients’ normal skin had many similarities, but were quite different from the aged match group of women who had not had melanoma,” according to study author Brian Gastman, M.D., plastic surgeon and director of melanoma at Cleveland Clinic.
They found that miR-193b, miR-342-3p, miR186, miR-130a and miR-146a were among the miRNAs that were commonly and significantly down-regulated in the women with histories of melanoma.
“The types of mRNAs that were altered in expression allowed us to predict the type of proteins and ultimately molecular pathways that were altered in these seemingly normal appearing skin cells,” Dr. Gastman says.
By identifying mechanisms that are associated with normal appearing skin in patients with a history of melanoma, researchers may be able to identify a high-risk population that otherwise would only be identified once they have cancer, and the pathways, once fully validated, can be targeted to, hopefully, prevent the onset of skin cancer, Dr. Gastman says.
“We have already identified multiple molecular pathways and molecules that heretofore were not associated with melanoma. These will yield a multitude of potential scientific and translatable questions and studies,” he says.
The next step, according to Dr. Gastman, is to do further validation of these newly identified molecules and pathways and then test a group from the general population to assess their importance.
Disclosure: Dr. Gastman reports a consulting agreement with Castle Biosciences, although, he says, that relationship was not involved in this study.
1. Sha J, Gastman BR, Morris N, et al. The Response of microRNAs to Solar UVR in Skin-Resident Melanocytes Differs between Melanoma Patients and Healthy Persons. PLoS ONE. 2016;11(5):e0154915.