METTL16 通过 m6A 修饰调节 FBXO5 的 mRNA 稳定性,从而促进乳腺癌的恶性行为。

IF 6 3区 医学 Q1 CELL BIOLOGY
Runying Wang, Xingjie Gao, Luhan Xie, Jiaqi Lin, Yanying Ren
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引用次数: 0

摘要

背景:N6-甲基腺苷(m6AN6-甲基腺苷(m6A)调控乳腺癌(BC)的进展。我们旨在研究甲基转移酶样蛋白 16(METTL16)在乳腺癌生长和转移中的作用和机制:方法:采用 RT-qPCR、免疫印迹和 IHC 检测基因表达水平。采用 CCK-8、克隆形成、伤口愈合和透孔试验测定细胞的增殖、迁移和侵袭。m6A RNA 甲基化和 MeRIP 试验确认总 RNA 和 FBXO5 mRNA 的 m6A 水平。利用 RIP 法确定 METTL16 和 FBXO5 mRNA 之间的相互作用。为进一步证实 METTL16 的作用,构建了体内小鼠皮下肿瘤和转移模型:结果:METTL16在BC细胞和组织中过表达。结果:METTL16在BC细胞和组织中过表达,抑制METTL16可抑制BC的生长和转移。此外,在 BC 组织中,METTL16 的水平与 FBXO5 的水平呈正相关,METTL16 依赖于 m6A 修饰增强了 FBXO5 mRNA 的稳定性。FBXO5的过表达拮抗了METTL16敲除对BC细胞增殖、迁移、侵袭和EMT的抑制作用:结论:METTL16通过m6A修饰提高了FBXO5的mRNA稳定性,从而促进了BC在体外和体内的恶性作用,为治疗BC提供了新的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
METTL16 regulates the mRNA stability of FBXO5 via m6A modification to facilitate the malignant behavior of breast cancer.

Background: N6-methyladenosine (m6A) regulates the progression of breast cancer (BC). We aimed to investigate the action and mechanism involved of methyltransferase-like protein 16 (METTL16) in BC growth and metastasis.

Methods: RT-qPCR, immunoblotting, and IHC were performed to test the levels of gene expression. CCK-8, clone formation, wound healing, and transwell assays were applied to measure the cell proliferation, migration, and invasion. m6A RNA methylation and MeRIP assay were utilized to confirm the m6A level of total RNA and FBXO5 mRNA. RIP was utilized to ascertain the interaction between METTL16 and FBXO5 mRNA. The in vivo murine subcutaneous tumor and metastasis model were constructed to further confirm the action of METTL16.

Results: METTL16 was overexpression in BC cells and tissues. Inhibition of METTL16 restrained the growth and metastasis of BC. Furthermore, the METTL16 level and FBXO5 level was positively correlated in BC tissues, and METTL16 aggrandized the stability of FBXO5 mRNA depending on the m6A modification. Overexpression of FBXO5 antagonized the restrained function of METTL16 knockdown on BC cells' proliferation, migration, invasion, and EMT.

Conclusion: METTL16 boosts the mRNA stability of FBXO5 via m6A modification to facilitate the malignant action of BC in vitro and in vivo, offering new latent targets for cure of BC.

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来源期刊
自引率
1.70%
发文量
17
审稿时长
14 weeks
期刊介绍: Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.
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