Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Department of Medical Research, Jen-Ai Hospital, Taichung, Taiwan, Republic of China.
Sci Rep. 2019 Feb 11;9(1):1771. doi: 10.1038/s41598-018-38394-6.
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 G/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.
蛋白质精氨酸甲基转移酶 1（PRMT1）催化形成非对称二甲基精氨酸，与癌症的发生、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）细胞表现出生长速度降低和 G/M 期细胞周期停滞。它们还表现出衰老表型和 p53 表达增加。p21 和 PAI-1 是 p53 下游两个对衰老至关重要的靶标，在接受 PRMT1-KD 或抑制剂处理的 SK-N-SH 细胞中显著诱导。诱导被 p53 抑制剂抑制，在 p53 缺失的 SK-N-AS 细胞系中抑制作用较弱，表明对 p53 的依赖性。总的来说，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作用。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，并表明 PRMT1 作为神经母细胞瘤生物学调节剂的多面复杂性。
