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- 05/25/2016

Skin cancer could be prevented with ‘sunscreen gene’

H&PC Today

Senior author Chengyu Liang, of the Keck School of Medicine at the University of Southern California (USC), and colleagues publish their findings in the journal Molecular Cell.

Skin cancer is the most common form of cancer among men and women in the United States.

According to the American Cancer Society, every year, around 3.3 million Americans are diagnosed with basal and squamous cell skin cancers, and around 76,380 Americans are diagnosed withmelanoma skin cancer – the deadliest form.

The Skin Cancer Foundation state that ultraviolet (UV) radiation isconsidered the primary cause of basal and squamous cell skin cancers, while Liang and colleagues note that UV exposure is the cause of more than 90 percent of melanoma skin cancers.

UV radiation – from sunlight and tanning beds and lamps – damages the DNA of skin cells, which can cause genetic mutations that lead to skin cancer.

But in the new study, the researchers reveal the discovery of a gene that appears to protect against the effects of UV-related skin cell damage, paving the way for a possible preventive strategy for skin cancer.

For their study, Liang and colleagues investigated the function of the UV radiation resistance-associated gene (UVRAG).

Previous research has suggested the gene plays a role in a disease called xeroderma pigmentosum, which increases sensitivity to sunlight, raising the risk for skin cancer.

However, the role of UVRAG among healthy individuals and those with skin cancer has been unclear.

Researchers found a gene called UVRAG repairs damage called by UV radiation.

UV damage repair reduced with abnormal UVRAG
In this latest research, the team analyzed human melanoma cells and those of a fruit fly model. Each group had either reduced levels of UVRAG or a mutated copy of the gene.

Human and fruit fly melanoma cells with normal copies of the UVRAG gene were also assessed.

On administering a shot of UV radiation to the cells, the team found those that possessed the normal UVRAG gene had more than 50 percent of the damage caused by UV radiation repaired within 24 hours.

However, cells that had reduced levels of UVRAG or had a mutated version of the gene only had around 20 percent of the UV-related damage repaired.

Furthermore, on analyzing genetic data of individuals with melanoma, the team found that those with lower levels of UVRAG had more advanced forms of the disease and a lower survival rate.

UVRAG could be a target for skin cancer prevention
The researchers say their results shed light on the function of UVRAG, revealing that it is involved in the DNA-cell repair process in response to damage caused by UV radiation.

When cell damage from UV radiation occurs, a known protein searches for lesions. When it identifies these lesions, the protein “tags” the UVRAG gene, encouraging it to initiate the DNA repair process.

However, when levels of UVRAG are reduced or the gene is mutated, the DNA process does not occur.

“The UV-resistant gene is a tumor suppressor involved in the UV-repair process of a cell’s DNA and is essential for preventing UV-induced genomic instability,” explains lead author Yongfei Yang, of the Keck School of Medicine at USC. “When the UV-resistant gene is lost, the cell cannot efficiently repair UV- and chemical-induced damage.”

Overall, the researchers say their findings indicate that UVRAG may be a promising target for skin cancer prevention.