PRMT1 promotes neuroblastoma cell survival through ATF5.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
15 May 2020
15 May 2020
Historique:
received:
13
12
2019
accepted:
05
05
2020
revised:
04
05
2020
entrez:
17
5
2020
pubmed:
18
5
2020
medline:
18
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32415090
doi: 10.1038/s41389-020-0237-9
pii: 10.1038/s41389-020-0237-9
pmc: PMC7229216
doi:
Types de publication
Journal Article
Langues
eng
Pagination
50Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM126154
Pays : United States
Références
Guccione, E. & Richard, S. The regulation, functions and clinical relevance of arginine methylation. Nat. Rev. Mol. Cell Biol. 20, 642–657 (2019).
Yang, Y. & Bedford, M. T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer 13, 37–50 (2013).
Eberhardt, A. et al. Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma. Oncotarget 7, 63629–63639 (2016).
doi: 10.18632/oncotarget.11556
Park, J. H. et al. Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells. Mol. Oncol. 9, 617–627 (2015).
doi: 10.1016/j.molonc.2014.10.015
Louis, C. U. & Shohet, J. M. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev. Med. 66, 49–63 (2015).
doi: 10.1146/annurev-med-011514-023121
Valentijn, L. J. et al. Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification. Proc. Natl Acad. Sci. USA 109, 19190–19195 (2012).
doi: 10.1073/pnas.1208215109
Liu, M. et al. Transcriptional profiling reveals a common metabolic program in high-risk human neuroblastoma and mouse neuroblastoma sphere-forming cells. Cell Rep. 17, 609–623 (2016).
doi: 10.1016/j.celrep.2016.09.021
Li, X. et al. H4R3 methylation facilitates beta-globin transcription by regulating histone acetyltransferase binding and H3 acetylation. Blood 115, 2028–2037 (2010).
doi: 10.1182/blood-2009-07-236059
Sears, T. K. & Angelastro, J. M. The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer. Oncotarget 8, 84595–84609 (2017).
doi: 10.18632/oncotarget.21102
Banerjee, D. et al. Activating transcription factor 5 (ATF5) in highly expressed in Stage 4, MYCN-amplified neuroblastoma. Cancer Res. 75, Abstract no. 1946 (2015).
Banerjee, D. et al. A novel cell-penetrating ATF5 antagonist peptide CPd/n-ATF5 exerts in vitro and in vivo anti-tumor effects in a broad spectrum of pediatric cancers. Cancer Res. 77, Abstract no. 702 (2017).
Huang, S., Li, X., Yusufzai, T. M., Qiu, Y. & Felsenfeld, G. USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier. Mol. Cell Biol. 27, 7991–8002 (2007).
doi: 10.1128/MCB.01326-07
Bao, X. et al. CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue. Dev. Cell 43, 227–239 (2017).
doi: 10.1016/j.devcel.2017.08.021
Tewary, S. K., Zheng, Y. G. & Ho, M. C. Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level. Cell Mol. Life Sci. 76, 2917–2932 (2019).
Zhang, J. et al. Discovery of Decamidine as a New and Potent PRMT1 Inhibitor. Medchemcomm 8, 440–444 (2017).
doi: 10.1039/C6MD00573J
Yan, L. et al. Diamidine compounds for selective inhibition of protein arginine methyltransferase 1. J. Med. Chem. 57, 2611–2622 (2014).
doi: 10.1021/jm401884z
Yu, X. R. et al. Discovery and structure-activity analysis of 4-((5-nitropyrimidin-4-yl)amino)benzimidamide derivatives as novel protein arginine methyltransferase 1 (PRMT1) inhibitors. Bioorg. Med. Chem. Lett. 25, 5449–5453 (2015).
doi: 10.1016/j.bmcl.2015.06.095
Zhang, W. Y. et al. Discovery of alkyl bis(oxy)dibenzimidamide derivatives as novel protein arginine methyltransferase 1 (PRMT1) inhibitors. Chem. Biol. Drug Des. 90, 1260–1270 (2017).
doi: 10.1111/cbdd.13047
Hansen, J. N. et al. Using chemistry to target neuroblastoma. ACS Chem. Neurosci. 8, 2118–2123 (2017).
doi: 10.1021/acschemneuro.7b00258
Bissinger, E. M. et al. Acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hPRMT1. Bioorg. Med. Chem. 19, 3717–3731 (2011).
doi: 10.1016/j.bmc.2011.02.032
Mitchell, L. H. et al. Aryl pyrazoles as potent inhibitors of arginine methyltransferases: identification of the first PRMT6 tool compound. ACS Med. Chem. Lett. 6, 655–659 (2015).
doi: 10.1021/acsmedchemlett.5b00071
Dhar, S. et al. Loss of the major Type I arginine methyltransferase PRMT1 causes substrate scavenging by other PRMTs. Sci. Rep. 3, 1311 (2013).
doi: 10.1038/srep01311
Gao, G. et al. PRMT1 loss sensitizes cells to PRMT5 inhibition. Nucleic. Acids Res. 47, 5038–5048 (2019).
Fong, J. Y. et al. Therapeutic targeting of RNA splicing catalysis through inhibition of protein arginine methylation. Cancer Cell. 36, 194–209 (2019).
Fedoriw, A. et al. Anti-tumor activity of the type I PRMT inhibitor, GSK3368715, synergizes with PRMT5 inhibition through MTAP loss. Cancer Cell. 36, 100–114 (2019).
Weiss, W. A., Aldape, K., Mohapatra, G., Feuerstein, B. G. & Bishop, J. M. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J. 16, 2985–2995 (1997).
doi: 10.1093/emboj/16.11.2985
Lee, Y. J. et al. Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells. Sci. Rep. 9, 1771 (2019).
Ross, R. A., Spengler, B. A. & Biedler, J. L. Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J. Natl Cancer Inst. 71, 741–747 (1983).
van Groningen, T. et al. A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma. Nat. Commun. 10, 1530 (2019).
doi: 10.1038/s41467-019-09470-w
Favia, A. et al. The protein arginine methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells. Sci. Rep. 9, 15925 (2019).
Eleveld, T. F. et al. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat. Genet. 47, 864–871 (2015).
doi: 10.1038/ng.3333
Schramm, A. et al. Mutational dynamics between primary and relapse neuroblastomas. Nat. Genet. 47, 872–877 (2015).
doi: 10.1038/ng.3349
van de Wetering, M. et al. Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector. EMBO Rep. 4, 609 (2003).
doi: 10.1038/sj.embor.embor865
Angelastro, J. M. et al. Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. J. Neurosci. 23, 4590–4600 (2003).
doi: 10.1523/JNEUROSCI.23-11-04590.2003
Haraguchi, S. & Nakagawara, A. A simple PCR method for rapid genotype analysis of the THMYCN transgenic mouse. PLoS ONE 4, e6902 (2009).
doi: 10.1371/journal.pone.0006902
Hansen, J. N., Lotta, L. T., Eberhardt, A., Schor, N. F. & Li, X. EYA1 expression and subcellular localization in neuroblastoma and its association with prognostic markers. J. Cancer Res. Ther. 4, 11–18 (2016).
doi: 10.14312/2052-4994.2016-3
Yu, G., Wang, L., Han, Y. & He, Q. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
doi: 10.1089/omi.2011.0118
Walter, W., Sanchez-Cabo, F. & Ricote, M. GOplot: an R package for visually combining expression data with functional analysis. Bioinformatics 31, 2912–2914 (2015).
doi: 10.1093/bioinformatics/btv300