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IGFBP6 敲低对 MDA-MB-231 细胞系中调节外泌体合成和分泌的蛋白质的影响。

Effect of IGFBP6 Knockdown on Proteins Regulating Exosome Synthesis and Secretion in MDA-MB-231 Cell Line.

机构信息

Faculty of Biology and Biotechnologies, National Research University Higher School of Economics, Moscow, Russia.

Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2023 May;175(1):157-161. doi: 10.1007/s10517-023-05828-9. Epub 2023 Jun 19.

Abstract

One of the potential causes of cancer recurrence is disruption of the cell-cell communication in the primary tumors that is realized, among other things, through secretion and uptake of exosomes by cells. Low expression of the IGFBP6 gene (insulin-like growth factor binding protein 6) is associated with a high recurrence rate and can serve as a prognostic marker of luminal breast cancer. The knockdown of the IGFBP6 gene leads to significant changes in lipid metabolism. We performed a quantitative analysis of both exosomes and proteins involved in the mechanism of their biogenesis. Changes in the expression profile of mRNAs and their proteins responsible for the synthesis and secretion of exosomes were revealed. We showed a decrease in the expression of the of the VPS28 gene mRNA (vacuolar protein sorting-associated protein 28) and the corresponding protein by 2.3 and 5.6 times, respectively. The secretion of exosomes by MDA-MB-231 cells with IGFBP6 knockdown decreased by 2 times. We discussed a mechanism of disruption of cell-cell communication.

摘要

癌症复发的一个潜在原因是原发性肿瘤中细胞间通讯的中断,这主要通过细胞分泌和摄取外泌体来实现。IGFBP6 基因(胰岛素样生长因子结合蛋白 6)表达水平低与复发率高有关,可作为腔型乳腺癌的预后标志物。IGFBP6 基因的敲低导致脂质代谢发生显著变化。我们对参与外泌体生物发生机制的外泌体和蛋白质进行了定量分析。揭示了参与外泌体合成和分泌的 mRNA 及其蛋白质表达谱的变化。我们发现 VPS28 基因 mRNA(液泡蛋白分选相关蛋白 28)及其相应蛋白的表达分别降低了 2.3 倍和 5.6 倍。IGFBP6 敲低的 MDA-MB-231 细胞分泌的外泌体减少了 2 倍。我们讨论了细胞间通讯中断的机制。

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