Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells
Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells
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DOI：
10.1038/s41598-018-38394-6
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发表时间：
2019-02-11
影响因子：
4.6
通讯作者：
Li, Chuan
中科院分区：
文献类型：
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作者：
Lee, Yu-Jen;Chang, Wen-Wei;Li, Chuan
蛋白质精氨酸甲基转移酶 1 (PRMT1) 催化不对称二甲基精氨酸的形成，与癌症的发展、转移和预后有关。在这项研究中，我们研究了低 PRMT1 水平对非 MYCN 扩增的神经母细胞瘤 SK-N-SH 细胞系的影响。稳定的 PRMT1 敲低 (PRMT1-KD) 细胞表现出生长速率降低和细胞周期停滞在 G2/M 期。它们还表现出衰老表型和 p53 表达增加。 p21 和 PAI-1 是对衰老至关重要的两个 p53 下游靶标，在接受 PRMT1-KD 或抑制剂处理的 SK-N-SH 细胞中显着诱导。这种诱导被 p53 抑制剂抑制，并且在 p53 缺失的 SK-N-AS 细胞系中处于边缘状态，表明对 p53 的依赖。总体而言，PRMT1-KD SK-N-SH 细胞的 DNA 损伤和 ROS 水平略有增加。它们的迁移活性也随着 PAI-1 的诱导而增加。因此，PRMT1 下调释放了 SK-N-SH 细胞中细胞衰老和迁移活性的抑制。这些结果可能部分解释了非 MYCN 扩增队列中低 PRMT1 的不良预后结果，并表明 PRMT1 作为神经母细胞瘤的生物调节剂的多方面复杂性。
Protein arginine methyltransferase 1 (PRMT1) catalyzing the formation of asymmetric dimethylarginines has been implicated in cancer development, metastasis, and prognosis. In this study, we investigated the effects of low PRMT1 levels on a non-MYCN amplified neuroblastoma SK-N-SH cell line. Stable PRMT1-knockdown (PRMT1-KD) cells showed reduced growth rates and cell cycle arrest at G2/M. They also exhibited senescent phenotypes and increased p53 expression. p21 and PAI-1, which are two p53 downstream targets critical for senescence, were significantly induced in SK-N-SH cells subjected to either PRMT1-KD or inhibitor treatment. The induction was suppressed by a p53 inhibitor and marginal in a p53-null SK-N-AS cell line, suggesting dependence on p53. In general, the DNA damage and ROS levels of the PRMT1-KD SK-N-SH cells were slightly increased. Their migration activity also increased with the induction of PAI-1. Thus, PRMT1 downregulation released the repression of cellular senescence and migration activity in SK-N-SH cells. These results might partially explain the poor prognostic outcome of low PRMT1 in a non-MYCN-amplified cohort and indicate the multifaceted complexity of PRMT1 as a biological regulator of neuroblastoma.