期刊
CELL DEATH AND DIFFERENTIATION
卷 28, 期 9, 页码 2818-2836出版社
SPRINGERNATURE
DOI: 10.1038/s41418-021-00786-z
关键词
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资金
- National Natural Science Foundation of China [81773017, 41931291, 81802816, 81902882]
- Ministry of Science and Technology of China [2016YFA0102400]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT310027]
- Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-1-003]
The PRMT5/Snail complex plays a crucial role in promoting invasion and metastasis of cervical cancer by targeting genes related to EMT, while the PRMT5 inhibitor EPZ015666 suppresses the invasion potential of cervical cancer cells by disinhibiting the expression of TET1 and increasing 5hmC levels, suggesting PRMT5 as a potential target for cancer therapy.
The biological function of PRMT5 remains poorly understood in cervical cancer metastasis. Here, we report that PRMT5 physically associates with the transcription factor Snail and the NuRD(MTA1) complex to form a transcriptional-repressive complex that catalyzes the symmetrical histone dimethylation and deacetylation. This study shows that the Snail/PRMT5/NuRD(MTA1) complex targets genes, such as TET1 and E-cadherin, which are critical for epithelial-mesenchymal transition (EMT). This complex also affects the conversion of 5mC to 5hmC. This study demonstrates that the Snail/PRMT5/NuRD(MTA1) complex promotes the invasion and metastasis of cervical cancer in vitro and in vivo. This study also shows that PRMT5 expression is upregulated in cervical cancer and various human cancers, and the PRMT5 inhibitor EPZ015666 suppresses EMT and the invasion potential of cervical cancer cells by disinhibiting the expression of TET1 and increasing 5hmC, suggesting that PRMT5 is a potential target for cancer therapy.
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