Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells

• Published in: Scientific reports Vol. 9; no. 1; p. 1771
• Main Authors: Lee, Yu-Jen, Chang, Wen-Wei, Chang, Chien-Ping, Liu, Tsung-Yun, Chuang, Chun-Yi, Qian, Kun, Zheng, Y. George, Li, Chuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.02.2019; Nature Publishing Group
• Subjects: 13; 14; 14/1; 38; 38/1; 38/77; 631/80/458/1648; 631/80/509; Arginine; Cancer; Cell cycle; DNA damage; Growth rate; Humanities and Social Sciences; Metastases; multidisciplinary; Neuroblastoma; p53 Protein; Phenotypes; Protein arginine methyltransferase; Science; Science (multidisciplinary); Senescence
• ISSN: 2045-2322; 2045-2322
• 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 2 /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.