Snail/PRMT5/NuRD complex contributes to DNA hypermethylation in cervical cancer by TET1 inhibition.
Animals
DNA Methylation
/ genetics
Epigenomics
/ methods
Female
Humans
Mice
Mice, Nude
Mixed Function Oxygenases
/ antagonists & inhibitors
Proto-Oncogene Proteins
/ antagonists & inhibitors
Signal Transduction
Snail Family Transcription Factors
/ genetics
Transfection
/ methods
Uterine Cervical Neoplasms
/ genetics
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
15
09
2020
accepted:
15
04
2021
revised:
08
04
2021
pubmed:
7
5
2021
medline:
22
3
2022
entrez:
6
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33953349
doi: 10.1038/s41418-021-00786-z
pii: 10.1038/s41418-021-00786-z
pmc: PMC8408166
doi:
Substances chimiques
Proto-Oncogene Proteins
0
Snail Family Transcription Factors
0
Mixed Function Oxygenases
EC 1.-
TET1 protein, human
EC 1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2818-2836Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81902882
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81802816
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81773017
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 41931291
Organisme : Chinese Ministry of Science and Technology | Department of S and T for Social Development (Department of S&T for Social Development)
ID : 2016YFA0102400
Informations de copyright
© 2021. The Author(s).
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