Transcriptomic analysis of melanoma cells reveals an association of a-synuclein with regulation of the inflammatory response

The Parkinson's disease protein, alpha-synuclein (a-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of a-syn's involvement in melanoma pathogenesis. To decipher the genes and pathways affected by a-syn, we conducted an RNA sequencing analysis of human SK-MEL-28 cells and several SK-MEL-28 SNCA-KO clones. We identified 1098 significantly up-regulated genes and 660 significantly down-regulated genes. Several of the upregulated genes are related to the immune system, i.e., the inflammatory response and the matrisome. We validated five upregulated genes (IL-1ý, SAA1, IGFBP5, CXCL8, and CXCL10) by RT-qPCR and detected IGFBP5 and IL-1ý in spent media of control and SNCA-KO cells. The levels of each of these secreted proteins were significantly higher in the spent media of the SNCA-KO clones than control cells. We suggest that the loss of a-syn expression unleashes chemokine/cytokine secretion, which could help melanoma cells evade the immune system. Overall design: SKMEL28 WT vs SNCA-KO