“Knowing these changes, we can potentially take biopsies from patients who’ve had melanoma or are at risk for melanoma and tell them, ‘You have changes at the genetic level of your skin that should concern you.’ In the general population of patients who’ve never had skin cancer, we could predict who may be at risk.”

Researchers identified 36 UV-miRNAs that had significant declines in concentration level in all 9 of the women with a history of melanoma. Of those, there were 17 microRNAs including miR-186 (P < .007), let-7a-5p (P < .003), and miR-29a (P < .003) whose expression was reported to be reduced or diminished in melanoma tissue.


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Researchers built several UV-microRNA-gene regulatory networks and a list of parameters describing the targeting efficiency of the UV-miRNAs in each. Four of these interlinked networks were indicative of EMT-like activities.

The first EMT-like network included 18 repressed UV-microRNA  that are connected to genes intrinsic to EMT-signaling pathways, which are known for their activities in responding to extracellular cues. Researchers noted that contained in this network were the NOTCH1, NOTCH2, WNT3a, and WNT5a genes, each of which was associated with at least 2 UV-miRNAs that can specifically target the gene in question.

The second EMT-like network consists of 21 UV-miRNAs and intersects with major EMT-inducing transcription factors such as ZEB (ZEB1/ZEB2), TWIST, SNAIL (SNAIL1/SNAIL2), and TBX3, all of which are known to repress transcription.

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“We don’t know who the next patient with melanoma is going to be,” Dr Gastman concluded. “But, by using this information, we could potentially make a prediction through biopsy. The goal is taking this specific microRNA information and the proteins they regulate to create a drug that can manipulate them back to being normal again.”

Reference

  1. Sha J, Gastman BR, Morris N, Mesinkovska NA, Baron ED, Cooper KD, et al. The response of microRNAs to solar UVR in skin-resident melanocytes differs between melanoma patients and healthy persons [published online ahead of print May 5, 2016]. PLoS One. doi: 10.1371/journal.pone.0154915.