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YTHDF3 facilitates triple-negative breast cancer progression and metastasis by stabilizing ZEB1 mRNA in an m(6)A-dependent manner

BACKGROUND: The YTH domain family protein 3 (YTHDF3) is an important N6-methyladenosine (m(6)A) reader which is involved in multiple cancers. However, the biological role and mechanisms of action for YTHDF3 in triple-negative breast cancer (TNBC) remains to be elucidated. METHODS: The expression of...

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Detalles Bibliográficos
Autores principales: Lin, Yuxiang, Jin, Xuan, Nie, Qian, Chen, Minyan, Guo, Wenhui, Chen, Lili, Li, Yan, Chen, Xiaobin, Zhang, Wenzhe, Chen, Hanxi, Jiang, Meichen, Xiao, Han, Zhang, Jie, Fu, Fangmeng, Wang, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848410/
https://www.ncbi.nlm.nih.gov/pubmed/35282088
http://dx.doi.org/10.21037/atm-21-6857
Descripción
Sumario:BACKGROUND: The YTH domain family protein 3 (YTHDF3) is an important N6-methyladenosine (m(6)A) reader which is involved in multiple cancers. However, the biological role and mechanisms of action for YTHDF3 in triple-negative breast cancer (TNBC) remains to be elucidated. METHODS: The expression of YTHDF3 in TNBC tissues was evaluated using The Cancer Genome Atlas (TCGA) database, BC-GenExMiner, and immunohistochemistry (IHC) staining. Cell migration, invasion, and epithelial-mesenchymal transition (EMT) were validated by wound healing assays, transwell assays, and Western blot (WB) analyses. The association between YTHDF3 and zinc finger E-box-binding homeobox 1 (ZEB1) was confirmed by Pearson correlation analysis. RNA-binding protein immunoprecipitation (RIP) assays and mRNA actinomycin stability analyses were applied to confirm whether YTHDF3 could interact with ZEB1in an m(6)A-dependent manner. RESULTS: The expression of YTHDF3 was correlated with poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Functional experiments indicated that YTHDF3 positively regulated cell migration, invasion, and EMT in TNBC cells. Moreover, ZEB1 was identified as a key downstream target for YTHDF3 and YTHDF3 could enhance ZEB1 mRNA stability in an m(6)A-dependent manner. Inhibition of YTHDF3 reduced migration, invasion, and EMT, all of which were reversed by rescue experiments overexpressing ZEB1. CONCLUSIONS: The findings herein confirmed that the YTHDF3/ZEB1 axis plays an important role in the progression and metastasis of TNBC. YTHDF3 is a promising prognosis biomarker and potential therapeutic target for patients with TNBC.