METTL3 regulates ferroptosis and malignant progression of cervical cancer cells through mediating TRPM7 methylation
10.16352/j.issn.1001-6325.2025.10.1318
- VernacularTitle:METTL3通过介导TRPM7甲基化调节宫颈癌细胞铁死亡和恶性进展
- Author:
Miao FU
1
;
Peng LIU
;
Wen TIAN
;
Sha WANG
;
Xiaomei YIN
;
Hao LIU
;
Donghai WANG
Author Information
1. 保定市第二中心医院 妇产科,河北 保定 072750
- Keywords:
cervical squamous cell carcinoma;
transient receptor potential cation channel subfamily M member 7;
methyltransferase 3;
ferroptosis;
N6-methyladenosine
- From:
Basic & Clinical Medicine
2025;45(10):1318-1325
- CountryChina
- Language:Chinese
-
Abstract:
Objective Methyltransferase 3(METTL3)mediated N6-methyladenosine(m6A)methylation modifica-tion of transient receptor potential cation channel subfamily M member 7(TRPM7)regulates ferroptosis and malig-nant progression in cervical cancer(CESC).Methods Totally 40 patients with cervical cancer were collected.Cer-vical cancer tissues and adjacent normal tissues(≥3 cm from the edge of the tumor tissue)were sampled at opera-tion and then divided into experimental group and control group,respectively.RT-qPCR and Western blot were used to detect the differences in TRPM7 mRNA and protein expression between the two groups.TRPM7-interfering cell lines were constructed to investigate the effects of TRPM7 on CESC cells.Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine(EdU)assay and flow cytometry,respectively.Transwell chamber assays were employed to evaluate cell invasion and migration capabilities.The levels of ferroptosis in CESC cells were measured using kits for reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and Fe2+.Bioinformatics tools were utilized to predict methyltransferases associated with TRPM7.The interaction between METTL3 and TRPM7 was examined through RNA immunoprecipitation(RIP)and methylated RNA immunoprecip-itation quantitative PCR(Me-RIP qPCR).The effect of METTL3 on the stability of TRPM7 expression was assessed using actinomycin D assay.Results TRPM7 was highly expressed in CESC tissue and cells.Knockdown of TRPM7 significantly inhibited cell proliferation,promoted cell apoptosis,suppressed cell migration and invasion capabilities,and enhanced ferroptosis levels(P＜0.05).Bioinformatics predictions suggested that METTL3 might act as a methyltransferase for TRPM7.Interference with METTL3 gene expression significantly reduced TRPM7 pro-tein levels,decreased TRPM7 m6A modification levels,and impaired TRPM7 gene stability(P＜0.05).Conclusions METTL3 regulates CESC proliferation,apoptosis,migration,invasion,and ferroptosis by m6A meth-ylation modification of the TRPM7 gene.
