Human giant congenital melanocytic nevus exhibits potential proteomic alterations leading to melanotumorigenesis

Abstract

BackgroundA giant congenital melanocytic nevus (GCMN) is a malformation of the pigment cells. It is a distress to the patients for two reasons: one is disfigurement, and the other is the possibility of malignant changes. However, the underlying mechanisms of the development of GCMN and melanotumorigenesis in GCMN are unknown. Hence, the aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN.ResultsProteomic differences between GCMN (n = 3) and normal skin samples (n = 3) were analyzed by one-dimensional-liquid chromatography-tandem mass spectrometry Relative levels of the selected proteins were validated using western blot analysis. The biological processes associated with the abundance modified proteins were analyzed using bioinformatic tools. Among the 46 abundance modified proteins, expression of 4 proteins was significantly downregulated and expression of 42 proteins was significantly upregulated in GCMN compared to normal skin samples (p < 0.05). More importantly, 31% of the upregulated proteins were implicated in various cancers, with five proteins being specifically related with melanoma. The abundance modified proteins in GCMN were involved in the biological processes of neurotrophin signaling, melanosome, and downregulated of MTA-3 in ER-negative breast tumors. In particular, an increase in the expression of the 14-3-3 protein family members appeared to be associated with key cellular biological functions in GCMN. Western blot analysis confirmed the upregulation of 14-3-3epsilon, 14-3-3 tau, and prohibitin in GCMN.ConclusionThese findings suggest that GCMN exhibits potential proteomic alterations, which may play a role in melanotumorigenesis, and the significant alteration of 14-3-3 family proteins could be a key regulator of the biological pathway remodeling in GCMN.

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

“…LC-MS and a non-labeled peptide count protein quantification method were used to analyze the proteomes of rat hearts as described previously [ 35 36 ]. Heart proteins were separated via SDS-PAGE on a 12% polyacrylamide gel.…”

NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1α expression levels during hypoxia/reoxygenation injury

“…Rat heart proteomes were analyzed by LC-MS and the non-labeled peptide count protein quantification method as described previously [ 23 ]. Briefly, dissolved heart proteins were separated on a 12% polyacrylamide gel by SDS-PAGE.…”

Filaggrin-2

“…In solid tumor lysates of skin melanoma in a melanoma mouse model, several fi laggrin-2 peptides (mainly located within the repetitive region) were found [ 79 ], and a downregulation of fi laggrin-2 has been observed in another melanocyte-involved disease, the giant congenital melanocytic nevus [ 80 ]. In an approach to search for markers of atherosclerosis, a screening of atherosclerotic plaques by subtractive phage display identifi ed fi laggrin-2 among 21 other proteins [ 81 ].…”