Sulforaphane suppresses PRMT5/MEP50 function in epidermal squamous cell carcinoma leading to reduced tumor formation
PublisherOxford University Press
MetadataShow full item record
AbstractProtein arginine methyltransferase 5 (PRMT5) cooperates with methylosome protein 50 (MEP50) to arginine methylate histone H3 and H4 to silence gene expression, and increased PRMT5 activity is associated with enhanced cancer cell survival. We have studied the role of PRMT5 and MEP50 in epidermal squamous cell carcinoma. We show that knockdown of PRMT5 or MEP50 results in reduced H4R3me2s formation, and reduced cell proliferation, invasion, migration and tumor formation. We further show that treatment with sulforaphane (SFN), a cancer preventive agent derived from cruciferous vegetables, reduces PRMT5 and MEP50 level and H4R3me2s formation, and this is associated with reduced cell proliferation, invasion and migration. The SFN-dependent reduction in PRMT5 and MEP50 level requires proteasome activity. Moreover, SFN-mediated responses are partially reversed by forced PRMT5 or MEP50 expression. SFN treatment of tumors results in reduced MEP50 level and H4R3me2s formation, confirming that that SFN impacts this complex in vivo. These studies suggest that the PRMT5/MEP50 is required for tumor growth and that reduced expression of this complex is a part of the mechanism of SFN suppression of tumor formation. Copyright The Author 2017. Published by Oxford University Press.
SponsorsThis work was supported by grants from the Maryland Stem Cell Research Foundation (R.L.E.) and the National Institutes of Health (CA131074 and CA184027 to R.L.E.) and a pilot grant from the Greenebaum Cancer Center (P30 CA134274). Conflict of Interest Statement: None declared.
Keywordmethylosome protein 50
Adaptor Proteins, Signal Transducing--genetics
Carcinoma, Squamous Cell--drug therapy
Isothiocyanates--administration & dosage
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85028435554&doi=10.1093%2fcarcin%2fbgx044&partnerID=40&md5=dcfd00dfb95b54eb9bc7ecbe535b3620; http://hdl.handle.net/10713/11326
- A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression.
- Authors: Chen H, Lorton B, Gupta V, Shechter D
- Issue date: 2017 Jan 19
- Methylosome Protein 50 and PKCδ/p38δ Protein Signaling Control Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression.
- Authors: Saha K, Eckert RL
- Issue date: 2015 May 22
- Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype.
- Authors: Ezeka G, Adhikary G, Kandasamy S, Friedberg JS, Eckert RL
- Issue date: 2021 Apr 19
- MEP50/PRMT5 Reduces Gene Expression by Histone Arginine Methylation and this Is Reversed by PKCδ/p38δ Signaling.
- Authors: Saha K, Adhikary G, Eckert RL
- Issue date: 2016 Jan
- Histone H2A and H4 N-terminal tails are positioned by the MEP50 WD repeat protein for efficient methylation by the PRMT5 arginine methyltransferase.
- Authors: Burgos ES, Wilczek C, Onikubo T, Bonanno JB, Jansong J, Reimer U, Shechter D
- Issue date: 2015 Apr 10