PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma.

Abstract

Protein arginine methyltransferase 5 (PRMT5), a histone methyltransferase responsible for the symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s), is an enzyme that participates in tumor cell progression in a variety of hematological malignancies. However, the biological functions of PRMT5 in multiple myeloma (MM) and the underlying molecular mechanisms remain unclear. In this study, we conducted a bioinformatics analysis and found that PRMT5 expression was significantly upregulated in MM. In vitro and in vivo phenotypic experiments revealed that knockdown of PRMT5 expression enhanced cell pyroptosis in MM. Moreover, we found that CASP1 expression was negatively correlated with PRMT5 expression, and repressing PRMT5 expression rescued both the phenotype and expression markers (N-GSDMD, IL-1b, and IL-18). Inhibition of PRMT5 activity increased CASP1 expression and promoted MM cell pyroptosis. Finally, high expression of PRMT5 or low expression of CASP1 was correlated with poor overall survival in MM. Collectively, our results provide a mechanism by which PRMT5 regulates cell pyroptosis by silencing CASP1 in MM.

• Authors: Tian Xia, Ming Liu, Quan Zhao, Jian Ouyang, Peipei Xu, Bing Chen
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 10 Pg. 851 (09 16 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 34531375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Histones
• RNA, Messenger
• Arginine
• PRMT5 protein, human
• Protein-Arginine N-Methyltransferases
• Caspase 1

Topics

• Animals
• Arginine (metabolism)
• Caspase 1 (genetics, metabolism)
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Histones (metabolism)
• Humans
• Male
• Methylation
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Multiple Myeloma (enzymology, genetics, pathology)
• Multivariate Analysis
• Promoter Regions, Genetic (genetics)
• Protein-Arginine N-Methyltransferases (genetics, metabolism)
• Pyroptosis (genetics)
• RNA, Messenger (genetics, metabolism)
• Survival Analysis
• Treatment Outcome
• Up-Regulation (genetics)
• Mice