Skin cancer is the most common cancer in the United States. Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly. At Sanford-Burnham’s Lake Nona campus, Dr. Ranjan Perera’s lab is studying what causes melanocytes (pigment-producing skin cells) to divide abnormally, ultimately forming melanoma. In a study published today in the journal PLoS ONE, a team led by Dr. Perera and post-doctoral researcher Dr. Joseph Mazar show that melanocyte growth and the cancer’s ability to invade other tissue is at least partially controlled by abnormal expression of microRNAs (miRNAs) – small strands of genetic material that may play a major role in numerous diseases by interfering with proteinproduction.“We’ve identified one specific miRNA, called miR-211, that could be used not only as a novel diagnostic marker for early melanoma detection, but also as a therapeutic target,” explains Dr. Perera, associate professor in Sanford-Burnham’s RNA Biology Program and senior author of the study.
There are roughly eight million biopsies performed for skin-related diseases each year in the United Sates, but only a small fraction turn out positive for melanoma. Not only is the high number of biopsies a burden, but the rarity of melanoma makes it easy to miss. Dr. Perera and Dr. Mazar show that melanomas produce lower miR-211 levels than normal melanocytes, meaning it could be used to distinguish melanoma from non-cancerous irregularities.
“Our research revealed that, while highly expressed in pigment-producing melanocytes of the skin, miR-211 was almost categorically removed from every non-pigmented melanoma cell line we examined, as well as numerous late-stage melanoma patient samples,” says Dr. Mazar. “This discovery offers the possibility that miR-211 could be used as a novel biomarker for this disease, to assist in early diagnosis.”
Then, moving one step further than many miRNA studies, the researchers also identified the molecular mechanisms regulating miR-211 in melanoma. What does miR-211 do? At typical levels, this little RNA strand impairs a cell’s ability to make a protein called KCNMA1, which helps regulate the flow of potassium across the cell membrane. Without that damper, melanoma and a few other types of cancer produce higher levels of KCNMA1, which seems to increase cell proliferation and invasiveness. After seeing these results, it was a “no-brainer” (in Dr. Perera’s words) to feed melanoma cells extra miR-211. The treatment slowed cellular growth and reduced invasiveness.
“In the next stage of this research, we are working with Southwest Research Institute to coat miR-211 with nanoparticles that will further enhance their therapeutic potential,” Dr. Perera says. They are also working on several other miR-211 target genes that they believe play a major role in the development of melanoma in humans.
Mazar, J., DeYoung, K., Khaitan, D., Meister, E., Almodovar, A., Goydos, J., Ray, A., & Perera, R. (2010). The Regulation of miRNA-211 Expression and Its Role in Melanoma Cell Invasiveness PLoS ONE, 5 (11) DOI: 10.1371/journal.pone.0013779