FAT1 inhibits the proliferation of DLBCL cells via increasing the m6A modification of YAP1 mRNA.
Sci Rep
; 14(1): 11836, 2024 05 23.
Article
de En
| MEDLINE
| ID: mdl-38782965
ABSTRACT
Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3'UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3'UTR m6A modification by decreasing the activity of the TGFß-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3'UTR via the TGFß-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteurs de transcription
/
ARN messager
/
Régulation de l'expression des gènes tumoraux
/
Lymphome B diffus à grandes cellules
/
Régions 3' non traduites
/
Protéines adaptatrices de la transduction du signal
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Prolifération cellulaire
/
Protéines de signalisation YAP
Limites:
Humans
Langue:
En
Journal:
Sci Rep
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine