Reining in melanoma with MicroRNA

By Heather Buschman, Ph.D.
November 1, 2010

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.

Read more about this study in the Orlando Sentinel and the Los Angeles Times. Or watch Orlando’s Channel 6 news highlight the story below:

Original paper:
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

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About Author

Heather Buschman, Ph.D.

Heather was an SBP Communications staff member.



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