YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.
J Pineal Res
; 76(5): e13003, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39143673
ABSTRACT
RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
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Progressão da Doença
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Neoplasias de Próstata Resistentes à Castração
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Pineal Res
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China