AEG-1, also called MTDH, has oncogenic potential in numerous cancers and is considered a multifunctional modulator because of its involvement in developmental processes and inflammatory and degenerative brain diseases. However, the role of AEG-1 in astrocytes remains unknown. This study aimed to investigate proteins directly regulated by AEG-1 by analyzing their RNA expression patterns in astrocytes transfected with scramble shRNA and AEG-1 shRNA. AEG-1 knockdown down-regulated TWIK-1 mRNA. Real-time quantitative PCR (qPCR) and immunocytochemistry assays confirmed that AEG-1 modulates TWIK-1 mRNA and protein expression. Electrophysiological experiments further revealed that AEG-1 further regulates TWIK-1-mediated potassium currents in normal astrocytes. An RNA immunoprecipitation assay to determine how AEG-1 regulates the expression of TWIK-1 revealed that AEG-1 binds directly to TWIK-1 mRNA. Furthermore, TWIK-1 mRNA stability was significantly increased upon overexpression of AEG-1 in cultured astrocytes (p < 0.01). Our findings show that AEG-1 serves as an RNA-binding protein to regulate TWIK-1 expression in normal astrocytes.

中文翻译：

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AEG-1调节TWIK-1表达作为星形胶质细胞中的一种RNA结合蛋白。

AEG-1（也称为MTDH）在多种癌症中具有致癌作用，由于它参与了发育过程以及炎症性和变性性脑病，因此被认为是多功能调节剂。但是，AEG-1在星形胶质细胞中的作用仍然未知。这项研究旨在通过分析在加扰的shRNA和AEG-1 shRNA转染的星形胶质细胞中的RNA表达模式来研究由AEG-1直接调节的蛋白。AEG-1组合式下调TWIK-1 mRNA。实时定量PCR（qPCR）和免疫细胞化学测定证实AEG-1调节TWIK-1 mRNA和蛋白质表达。电生理实验进一步表明，AEG-1进一步调节正常星形胶质细胞中TWIK-1介导的钾电流。一项用于确定AEG-1如何调节TWIK-1表达的RNA免疫沉淀试验表明，AEG-1直接与TWIK-1 mRNA结合。此外，在培养的星形胶质细胞中过表达AEG-1后，TWIK-1 mRNA的稳定性显着提高（p <0.01）。我们的发现表明，AEG-1是一种RNA结合蛋白，可调节正常星形胶质细胞中TWIK-1的表达。