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SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters.
- Source :
-
Cell death & disease [Cell Death Dis] 2021 Jul 23; Vol. 12 (8), pp. 731. Date of Electronic Publication: 2021 Jul 23. - Publication Year :
- 2021
-
Abstract
- Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.<br /> (© 2021. The Author(s).)
- Subjects :
- Apoptosis genetics
Base Sequence
Carcinoma, Hepatocellular genetics
Cell Cycle genetics
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Gene Expression Regulation, Neoplastic
HEK293 Cells
Histone-Lysine N-Methyltransferase genetics
Histones metabolism
Humans
Liver Neoplasms genetics
Lysine metabolism
Methylation
Neoplasm Invasiveness
RNA, Messenger genetics
RNA, Messenger metabolism
Signal Transduction
Sphingosine-1-Phosphate Receptors metabolism
Tumor Stem Cell Assay
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Disease Progression
Histone-Lysine N-Methyltransferase metabolism
Liver Neoplasms metabolism
Liver Neoplasms pathology
Promoter Regions, Genetic
Sphingosine-1-Phosphate Receptors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 12
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 34301921
- Full Text :
- https://doi.org/10.1038/s41419-021-04009-8