Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, USA.
Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA.
Sci Rep. 2024 Nov 7;14(1):27140. doi: 10.1038/s41598-024-78777-6.
The 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-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-1β, SAA1, IGFBP5, CXCL8, and CXCL10) by RT-qPCR and detected IGFBP5 and IL-1β 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. These secreted proteins quite likely activate the immune response against SNCA-KO cells. We suggest that, conversely, high levels of α-syn expression in melanoma cells helps the cells evade the immune system by inhibiting the secretion of these immune activating factors.
帕金森病蛋白，α-突触核蛋白（α-syn/SNCA）在神经元和黑色素瘤中高度表达。本研究的目的是揭示α-syn 参与黑色素瘤发病机制的机制。为了解 α-syn 影响的基因和途径，我们对人 SK-MEL-28 细胞和几个 SK-MEL-28 SNCA-KO 克隆进行了 RNA 测序分析。我们鉴定了 1098 个显著上调的基因和 660 个显著下调的基因。一些上调的基因与免疫系统有关，即炎症反应和基质体。我们通过 RT-qPCR 验证了五个上调基因（IL-1β、SAA1、IGFBP5、CXCL8 和 CXCL10），并在对照和 SNCA-KO 细胞的培养上清液中检测到 IGFBP5 和 IL-1β。这些分泌蛋白在 SNCA-KO 克隆的培养上清液中的水平明显高于对照细胞。这些分泌蛋白很可能激活针对 SNCA-KO 细胞的免疫反应。我们认为，相反，黑色素瘤细胞中高水平的 α-syn 表达通过抑制这些免疫激活因子的分泌来帮助细胞逃避免疫系统。
