The feedback loop of METTL14 and USP38 regulates cell migration, invasion and EMT as well as metastasis in bladder cancer.
PLoS Genet
; 18(10): e1010366, 2022 10.
Article
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| MEDLINE
| ID: mdl-36288387
ABSTRACT
BACKGROUND:
Bladder cancer (BCa) is one of the most prevalent malignancies globally. Previous study has reported the inhibitory effect of methyltransferase-like 14 (METTL14) on BCa tumorigenesis, but its role in the cell migration, invasion and epithelial-mesenchymal transition (EMT) in BCa remains unknown. MATERIALS ANDMETHODS:
Quantitative real-time PCR (RT-qPCR) and western blot were applied to measure RNA and protein expression respectively. Cell migration, invasion and EMT were evaluated by wound healing, Transwell, and immunofluorescence (IF) assays as well as western blot of EMT-related proteins. In vivo experiments were performed to analyze metastasis of BCa. Mechanism investigation was also conducted to study METTL14-mediated regulation of BCa progression.RESULTS:
METTL14 overexpression prohibits BCa cell migration, invasion in vitro and tumor metastasis in vivo. METTL14 stabilizes USP38 mRNA by inducing N6-methyladenosine (m6A) modification and enhances USP38 mRNA stability in YTHDF2-dependent manner. METTL14 represses BCa cell migration, invasion and EMT via USP38. Additionally, miR-3165 inhibits METTL14 expression to promote BCa progression.CONCLUSIONS:
Our study demonstrated that METTL14 suppresses BCa progression and forms a feedback loop with USP38. In addition, miR-3165 down-regulates METTL14 expression to promote BCa progression. The findings may provide novel insight into the underlying mechanism of METTL14 in BCa progression.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
MicroARNs
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article