METTL5-mediated m⁶A modification of SLC7A11 promotes cervical cancer by inhibiting ferroptosis.

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology Pub Date : 2025-06-15 DOI:10.1016/j.biocel.2025.106822

Yujin Dong, Wei Chang, Bei Lu, Yuanyuan Li, Yuanhua Liu

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引用次数: 0

Abstract

Ferroptosis could suppress the viability of cervical cancer cells and trigger their death, thereby offering a unique perspective for exploring novel therapeutic approach for cervical cancer. Here, this study tried to explore the role of N⁶-methyladenosine (m⁶A) methyltransferase methyltransferase-like 5 (METTL5) on cervical cancer ferroptosis. Elevated METTL5 functioned as an oncogene in cervical cancer tumorigenesis by inhibiting the ferroptosis. Mechanistically, METTL5 was verified to target SLC7A11 and installed the m⁶A methylation on SLC7A11 mRNA. Moreover, YTHDF3 bound with the m⁶A site of SLC7A11 mRNA to enhance SLC7A11 mRNA stability. Rescue assays confirmed that METTL5/YTHDF3/SLC7A11 axis inhibited the ferroptosis of cervical cancer cells. In vivo, METTL5 silencing repressed the tumor growth of cervical cancer cells, as well as reducing the SLC7A11. In conclusion, these data inspired that METTL5-mediated m⁶A modification of SLC7A11 promoted cervical cancer by inhibiting ferroptosis, providing a novel insight for cervical cancer.

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mettl5介导的m6A修饰SLC7A11通过抑制铁下垂促进宫颈癌。

铁下垂可以抑制宫颈癌细胞的活力并引发其死亡，从而为探索宫颈癌的新治疗方法提供了独特的视角。本研究试图探讨n6 -甲基腺苷（m6A）甲基转移酶-甲基转移酶样5 （METTL5）在宫颈癌铁下垂中的作用。升高的METTL5通过抑制铁下垂在宫颈癌的肿瘤发生中发挥致癌基因的作用。在机制上，METTL5被证实靶向SLC7A11，并将m6A甲基化安装在SLC7A11 mRNA上。此外，YTHDF3结合SLC7A11 mRNA的m6A位点，增强SLC7A11 mRNA的稳定性。挽救实验证实METTL5/YTHDF3/SLC7A11轴抑制子宫颈癌细胞铁下垂。在体内，METTL5沉默抑制了宫颈癌细胞的肿瘤生长，并降低了SLC7A11。综上所述，这些数据启发了mettl5介导的m6A修饰SLC7A11通过抑制铁下垂促进宫颈癌，为宫颈癌提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Biochemistry & Cell Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

0.00%

发文量

124

审稿时长

19 days

期刊介绍： IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research. Topics of interest include, but are not limited to: -Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism -Novel insights into disease pathogenesis -Nanotechnology with implication to biological and medical processes -Genomics and bioinformatics