METTL3 Regulates the Proliferation,Migration,and Invasion of Uveal Melanoma Cell via Modifying m6A Methylation
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0409
- VernacularTitle:METTL3通过m6A甲基化修饰影响葡萄膜黑色素瘤细胞增殖、迁移和侵袭
- Author:
Meilan WANG
1
;
Tianqi ZHAO
1
;
Qi SHI
1
;
Lili HAO
1
;
Lian LIU
1
Author Information
1. 暨南大学附属第一医院眼科,广东 广州 510630
- Publication Type:Journal Article
- Keywords:
uveal melanoma;
methyltransferase-like protein 3;
N6-methyladenosine;
proliferation;
invasion
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(4):628-638
- CountryChina
- Language:Chinese
-
Abstract:
[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.
