PRMT1 promotes neuroblastoma cell survival through ATF5

Zhong Yan Hua, Jeanne N. Hansen, Miao He, Shang Kun Dai, Yoonjung Choi, Melody D. Fulton, Sarah M. Lloyd, Marianna Szemes, Ji Sen, Han Fei Ding, James M. Angelastro, Xiang Fei, Hui Ping Li, Chao Ran Wu, Sheng Yong Yang, Karim Malik, Xiaomin Bao, Y. George Zheng, Chang Mei Liu, Nina F. SchorZhi Jie Li, Xing Guo Li

Research output: Contribution to journalArticlepeer-review

Abstract

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor of the sympathetic nervous system. Here, we demonstrate a critical role for PRMT1 in neuroblastoma cell survival. PRMT1 depletion decreased the ability of murine neuroblastoma sphere cells to grow and form spheres, and suppressed proliferation and induced apoptosis of human neuroblastoma cells. Mechanistic studies reveal the prosurvival factor, activating transcription factor 5 (ATF5) as a downstream effector of PRMT1-mediated survival signaling. Furthermore, a diamidine class of PRMT1 inhibitors exhibited anti-neuroblastoma efficacy both in vitro and in vivo. Importantly, overexpression of ATF5 rescued cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically. Taken together, our findings shed new insights into PRMT1 signaling pathway, and provide evidence for PRMT1 as an actionable therapeutic target in neuroblastoma.

Original languageEnglish (US)
Article number50
JournalOncogenesis
Volume9
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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