METTL14 inhibits the proliferation, migration and invasion of prostate cancer cells by increasing m6A methylation of CDK4.
Transl Androl Urol
; 13(7): 1145-1163, 2024 Jul 31.
Article
de En
| MEDLINE
| ID: mdl-39100843
ABSTRACT
Background:
Methyltransferase-like (METTL) plays an important role in various biological processes, but its role in prostate cancer (PCa) is still unclear. This study aimed to explore the mechanism by which methyltransferase-like 14 (METTL14) inhibits the physiological activity of PCa cells by increasing the N6-methyladenosine (m6A) modification of cyclin-dependent kinase 4 (CDK4).Methods:
Clinical samples were collected for bioinformatics analysis. A PCa mouse model was constructed. Cell counting kit-8 (CCK-8), flow cytometry, colony formation assays, scratch assays, Transwell assays, real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence and western blotting were used to detect the corresponding indicators.Results:
METTL14 was found to be beneficial to inhibit the proliferation, invasion, and migration of PCa cells. When the m6A RNA increased, the half-life of CDK4 mRNA decreased after oe-METTL14 (overexpression of METTL14). Overexpression of CDK4 reversed the effect of oe-METTL14. Coimmunoprecipitation experiments revealed there were interactions between CDK4 and forkhead box M1 (FOXM1). Transfection of si-CDK4 was similar to transfection of oe-METTL14. After transfection with oe-FOXM1, the invasion and migration ability of cells increased, and cell apoptosis decreased. After transfection with si-FOXM1 alone, autophagy related 7 (ATG7) expression was significantly downregulated, and autophagy levels were reduced. The overexpression of ATG7 reversed the effect of si-FOXM1. The tumor volume and weight of the oe-METTL14 group mice were significantly reduced, and tumor proliferation was decreased in comparison to untreated tumor-bearing mice.Conclusions:
METTL14 inhibits the invasion and migration of PCa cells and induces cell apoptosis by inhibiting CDK4 stability and FOXM1/ATG7-mediated autophagy.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Transl Androl Urol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Chine