Summary
Background
The absence of melanocytes poses a challenge for long‐term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I–II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same.
Objectives
To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)‐induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets.
Methods
Genome‐wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next‐generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied.
Results
Our study found sirtuin1 (SIRT1), an NAD‐dependent deacetylase, to be a direct target of miR‐211 – the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX‐527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR‐211 mimic led to a significant increase in γ‐H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB‐mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR‐211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB‐induced CPDs in primary keratinocytes.
Conclusions
These findings establish a novel MALAT1–miR‐211–SIRT1 signalling axis that potentially confers protection to the ‘amelanotic’ keratinocytes in vitiligo.
Eruptive vellus hair cyst (EVHC) is a rare follicular developmental abnormality of the vellus hair follicles. They are usually seen in children, adolescents, or young adults and manifest as reddish-brown smooth papules most commonly involving the chest, limbs, and abdomen. An 18-year-old male presented with asymptomatic papules on the trunk and flexor aspect of both forearms for the past 2 years. There was no family history of similar lesions. His medical history was also not contributory. A clinical diagnosis of steatocystoma multiplex and chronic folliculitis was given, and a punch biopsy from the papule was performed and sent for histopathological examination. On microscopic examination, a final diagnosis of EVHC was rendered. The patient was advised topical treatment of retinoic acid cream (0.05%) for 6 months, and he is currently under follow-up period. Due to its rarity and resemblance to many similar entities, histopathological examination plays a major role in establishing a definite diagnosis and further proper management of the patient. We report this unusual case to generate awareness about this rarely diagnosed condition.
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