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Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

VIT75 is a 75-kDa melanocyte membrane antigen (Ag) that had been observed, but not identified until now. Its immunopathogenic role in vitiligo remains unknown. In this study, serological proteome analysis based on mass spectrometry was employed to identify VIT75. Three disparate 75-, 60-, and 45-kDa proteins on two-dimensional (2D) gel were, respectively, identified as lamin A, tyrosinase-related protein 1, and melanin-concentrating hormone receptor 1. The latter two proteins are well-known Ags. Immunoreactivity analysis showed that the 75-kDa protein displayed on the 2D gel was recognized by human anti-lamin A IgG. Antibody (Ab) reactivity to lamin A was positive in 28.6% of patients' sera. Only 3.1% healthy sera reacted with the lamin A. A total of 91.7% of the positive sera was from the active non-segmental vitiligo (NSV). The positive rate and mean titer of anti-lamin A Ab are higher for NSV with autoimmune disease than for NSV without autoimmune disease. These data demonstrate that VIT75 is lamin A. To our knowledge, this is a previously unreported vitiligo Ag. Anti-lamin A Ab may be a potential marker of NSV with autoimmune disease. The study indicates that the targets of autoantibodies in vitiligo patients can be revealed by serological proteome analysis.