Epigenetic processes play a critical role in
melanoma development. However, little is known about
proteins responsible for epigenetic transformations in
melanoma cells. The processes in the peritumoral skin within the
excision margin are almost unstudied. We studied the changes in expression of 112
proteins involved in epigenetic regulation of gene expression in the human cutaneous
melanoma and its peritumoral zone using "The Proteomic Antibody Microarrays" (GRAA2, Sigma-Aldrich). Dimethylated
histone H3 at lysines 4 and 9 as well as
proteins involved in the regulation of transcription (
histone deacetylases HDAC-1 and HDAC-11,
DNA methyl-
binding protein Kaiso), cell cycle control (
protein kinases Aurora-В and PKR, chromosome
protein CENP-E , and phosphorylated and acetylated
histone H3), DNA repair (phosphorylated
histone H2AX), and
nuclear protein import (
importins α3 and α5/7) were over-expressed in the
melanoma tissue as compared with normal skin. At the same time, HDAC-10 and
proliferating cell nuclear antigen PCNA were downregulated. In the peritumoral skin, at the
excision margin (1-2 cm from the
melanoma edge), we observed similar changes in expression of these
proteins and, additionally, over-expression of
arginine methyltransferases PRMT5 and
NAD-dependent
histone deacetylase SIR2.
Histone methyltransferase G9a and
metastasis-associated
protein 2 were downregulated. Therefore, epigenetic regulation that requires histone modifications and expression of some regulatory
proteins is of importance for
melanoma development and propagation. The observed changes in the peritumoral skin may indicate the epigenetic pre-tuning in this zone possibly involved in malignant transformation. These results can be potentially useful for
melanoma diagnostics and targeted
therapy.