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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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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 |
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. |
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