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Understanding why patients with vitiligo rarely develop skin cancers
Publication year - 2021
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.20108
Subject(s) - vitiligo , skin cancer , dermatology , medicine , population , melanin , dark skin , cancer , biology , genetics , environmental health
Linked article: Brahmbhatt et al. Br J Dermatol 2021; 184 :1132–1142. Vitiligo is a common skin disorder affecting 0·2–2% of the world’s population. It occurs because of the loss of cells (melanocytes) responsible for producing melanin (the pigment that gives skin its characteristic colour) resulting in the affected skin appearing milky white. The presence of melanin pigment acts as a barrier to the harmful, cancer‐inducing sun’s rays [ultraviolet (UV) radiation]. However, surprisingly, despite the loss of melanin, people with vitiligo rarely develop skin cancers. This study from India aimed to find out the reason why. We obtained small skin samples from affected as well as the unaffected skin from five people who had vitiligo and extracted small pieces of genetic material known as microRNAs (miRNAs) from them. One miRNA – called miRNA‐211 was found to be present in very low quantities in vitiligo compared with the unaffected skin. We found that this miRNA could bind to another type of RNA called messenger RNA (mRNA) of the SIRT1 gene and prevent it from making the sirtuin1 (SIRT1) protein. Lower levels of miRNA‐211 in vitiligo skin meant less ‘stop signals’, leading to an increased expression of the SIRT1 protein. To understand whether the increased SIRT1 protein could protect the skin cells from sun‐induced damage, we treated keratinocytes (a type of skin cell) with a chemical that activated SIRT1 and we exposed these cells to UV radiation, mimicking sunlight exposure to the skin. Exposure of these treated keratinocytes to UV radiation showed a significant reduction in signs of DNA damage (cyclobutane pyrimidine dimers) as compared with cells with usual SIRT1 levels. Finally, we found that MALAT1, a long nonprotein coding RNA molecule, was highly expressed in vitiligo skin, and that it could bind to miRNA‐211 making it unavailable to bind to SIRT1 mRNA and therefore leading to increased SIRT1 protein expression, which protected the patient’s skin. Overall, this study found a novel molecular basis for the protection of vitiligo skin from sun‐induced damage.