Author:
Rajasekaran Santhanasabapathy,Cheng Siyuan,Gajendran Nithya,Shekoohi Sahar,Chesnokova Liudmila,Yu Xiuping,Witt Stephan N.
Abstract
AbstractThe Parkinson’s disease protein, alpha-synuclein (α-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of α-syn’s involvement in melanoma pathogenesis. To decipher the genes and pathways affected by α-syn, we conducted an RNA sequencing analysis of human SK-MEL-28 cells and several SK-MEL-28SNCA-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 andSNCA-KO cells. The levels of each of these secreted proteins were significantly higher in the spent media of theSNCA-KO clones than control cells. We suggest that the loss of α-syn expression unleashes chemokine/cytokine secretion, which could help melanoma cells evade the immune system.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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