Page 33 - CSIR-IGIB Annual Report 2020-21

Why do vitiligo patients rarely develop skin
cancer
Vitiligo occurs because of the loss of cells
(melanocytes) responsible for producing
melanin (the pigment that gives skin its
characteristic color) 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]. Surprisingly, despite the loss of
melanin, people with vitiligo rarely develop skin
cancers. We therefore investigated the
molecular mechanisms underlying this
conundrum. We obtained small skin samples
from affected as well as the unaffected skin
from five people who had vitiligo and extracted
small pieces of RNA 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 Overall, this study found that a novel molecular
unaffected skin. We found that this miRNA basis for the protection of vitiligo skin from sun-
could bind to another type of RNA called induced damage is MALAT1- miR-211-SIRT1
messenger RNA (mRNA) of the SIRT1 gene and signaling axis.
prevent it from making the sirtuin1 (SIRT1)
protein. Lower levels of miRNA-211 in vitiligo Delayed wound healing in vitiligo: Role of
skin meant less ‘stop signals’, leading to an miRNAs
increased expression of the SIRT1 protein. To Cutaneous wound healing requires a temporally
understand whether the increased SIRT1 coordinated communication between
protein could protect the skin cells from sun- keratinocytes, fibroblasts, and immune cells.
induced damage, we treated keratinocytes (a However, the role of melanocytes, the pigment-
type of skin cell) with a chemical that activated synthesizing cells in the epidermis, remains
SIRT1 and we exposed these cells to UV poorly explored. Thus, vitiligo, characterized by
radiation, mimicking sunlight exposure to the the selective loss of melanocytes, provided the
skin. Exposure of these treated keratinocytes to perfect opportunity to dissect their role in
UV radiation showed a significant reduction in influencing the kinetics of wound healing. The
signs of DNA damage (cyclobutane pyrimidine role of miRNAs is well established in skin
dimers) as compared with cells with usual SIRT1 development and pathology, including their
levels. Finally, we found that MALAT1, a long contribution in regulating wound healing. Thus,
non-protein coding RNA molecule, was highly we hypothesized that the loss of melanocytes
expressed in vitiligo skin, and that it could bind and/or its downstream effect(s) could be
to miRNA-211 making it unavailable to bind to causing a dysregulation of miRNAs, leading to a
SIRT1 mRNA and therefore leading to increased delay in re-epithelialization of lesional skin
SIRT1 protein expression, which protected the reported previously by our group. We
patient’s skin. performed a genome-wide miRnome of non-
lesional (NL) and lesional (L) skin on day1 (basal
level) as well as on day 14 (re-epithelialization
phase) and analysed the differentially expressed

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