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bioRxiv · 10.1101/2023.12.23.573196

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

Rajasekaran, S.·Cheng, S.·Gajendran, N.·Shekoohi, S.·Chesnokova, L.·Yu, X.·Witt, S. N.
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Abstract

The Parkinsons disease protein, alpha-synuclein (-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of -syns involvement in melanoma pathogenesis. To decipher the genes and pathways affected by -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-1y, SAA1, IGFBP5, CXCL8, and CXCL10) by RT-qPCR and detected IGFBP5 and IL-1y 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 -syn expression unleashes chemokine/cytokine secretion, which could help melanoma cells evade the immune system.

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Rajasekaran, S., Cheng, S., Gajendran, N., Shekoohi, S., Chesnokova, L., Yu, X., Witt, S. N.. 2023-12-23. Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response.. https://doi.org/10.1101/2023.12.23.573196

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