Researchers from the University of Chicago Medical Center identified a previously unknown molecular mechanism connecting sunburns with an elevated risk of developing skin cancer. In a paper released in the journal Nature Communications, scholars demonstrated that ultraviolet (UV) radiation destroys the protective protein YTHDF2, which has a central function in controlling inflammatory processes in the skin. This finding offers novel insight into how sun exposure might initiate long-term alterations leading to carcinogenesis.
Depletion of YTHDF2: The Trigger for Latent Inflammation
Until now, it was established that UV radiation damages DNA and causes oxidative stress, provoking the typical inflammatory response: redness, pain, and blistering. However, the new study led by Professor Yu-Ying He reveals a deeper chain of events. The scientists discovered that ultraviolet exposure sharply reduces the level of the YTHDF2 protein, responsible for regulating the activity of specific non-coding RNAs.
YTHDF2 recognizes modified RNA molecules (marked with m6A) and stops their interaction with immune receptors. Specifically, the protein prevents the activation of the TLR3 receptor—one of the key components of innate immunity, which normally does not participate in cutaneous inflammatory reactions. But when YTHDF2 levels fall due to UV radiation, non-coding RNAs, such as U6 snRNA, start activating TLR3 in endosomes, initiating a powerful inflammatory cascade.
This inflammatory reaction can be so intense that it causes cellular mutations and creates favorable conditions for the malignant transformation of skin tissues.
New Avenues for Prevention and Therapy
Understanding the function of YTHDF2 in suppressing excessive inflammation opens prospects for developing new strategies for skin cancer prevention and treatment. Maintaining YTHDF2 activity or pharmacologically blocking the TLR3 pathway after UV damage could become strategies to avert the acute inflammation’s transition to chronic and carcinogenic states.
The authors stress that about 90% of skin cancer instances are linked to exposure to ultraviolet radiation. Therefore, conventional prophylactic measures—regular use of sunscreen, avoiding excessive sun exposure, wearing protective apparel, and timely skin examination—remain critically important.
Nevertheless, the recent discovery provides an opportunity to move beyond external protection, suggesting paths for molecular intervention right at the onset of the inflammatory sequence. This may result in the creation of medications—in the form of creams, gels, or systemic agents—capable of modulating key molecules and lowering the risk of skin oncological diseases in their early developmental stages.
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