METTL3 promotes prostate cancer cell metastasis and EMT by mediating NUP210 m6A modification

IF 1.9 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2026-01-01 Epub Date: 2026-02-23 DOI:10.1016/j.mrfmmm.2026.111930

Shaoxing Wang, Jinming Li, Jun Jiang, Jiahao Liu, Shusen Zuo

{"title":"METTL3 promotes prostate cancer cell metastasis and EMT by mediating NUP210 m6A modification","authors":"Shaoxing Wang, Jinming Li, Jun Jiang, Jiahao Liu, Shusen Zuo","doi":"10.1016/j.mrfmmm.2026.111930","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is an age-related epithelial malignancy with high metastatic potential. Although nucleoporin 210 (NUP210) is implicated in tumor progression, its role and mechanism in PCa metastasis remain unexplored.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis (Gene Expression Omnibus (GEO)/The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases) and experimental validation (quantitative real-time PCR (qRT-PCR) and western blot) were applied to assess the expression of NUP210, methyltransferase-like 3 (METTL3), metastasis-related markers, and epithelial-mesenchymal transition (EMT)-related markers. Functional assays (transwell, <em>in vivo</em> metastasis models) and mechanistic studies (methylated RNA immunoprecipitation (MeRIP), RNA binding protein immunoprecipitation (RIP), and mRNA stability assays) were performed to elucidate the METTL3/NUP210 axis.</div></div><div><h3>Results</h3><div>NUP210 and METTL3 were highly expressed in PCa tissues and cells. Knockdown of NUP210 significantly inhibited PCa metastasis and EMT. Also, the animal study revealed that NUP210 silencing could inhibit the lung metastasis of PCa <em>in vivo</em>. METTL3-mediated N6-methyladenosine (m6A) modification stabilized NUP210 mRNA, and rescue experiments confirmed that NUP210 overexpression reversed the inhibitory effects of METTL3 silencing on PCa cell metastasis and EMT.</div></div><div><h3>Conclusion</h3><div>The METTL3-mediated m6A modification of NUP210 may promote PCa metastasis and EMT. This newly identified METTL3/NUP210 axis deepens the understanding of PCa progression and suggests its potential for further therapeutic exploration.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"832 ","pages":"Article 111930"},"PeriodicalIF":1.9000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1386196426000035","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/23 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Prostate cancer (PCa) is an age-related epithelial malignancy with high metastatic potential. Although nucleoporin 210 (NUP210) is implicated in tumor progression, its role and mechanism in PCa metastasis remain unexplored.

Methods

Bioinformatics analysis (Gene Expression Omnibus (GEO)/The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases) and experimental validation (quantitative real-time PCR (qRT-PCR) and western blot) were applied to assess the expression of NUP210, methyltransferase-like 3 (METTL3), metastasis-related markers, and epithelial-mesenchymal transition (EMT)-related markers. Functional assays (transwell, in vivo metastasis models) and mechanistic studies (methylated RNA immunoprecipitation (MeRIP), RNA binding protein immunoprecipitation (RIP), and mRNA stability assays) were performed to elucidate the METTL3/NUP210 axis.

Results

NUP210 and METTL3 were highly expressed in PCa tissues and cells. Knockdown of NUP210 significantly inhibited PCa metastasis and EMT. Also, the animal study revealed that NUP210 silencing could inhibit the lung metastasis of PCa in vivo. METTL3-mediated N6-methyladenosine (m6A) modification stabilized NUP210 mRNA, and rescue experiments confirmed that NUP210 overexpression reversed the inhibitory effects of METTL3 silencing on PCa cell metastasis and EMT.

Conclusion

The METTL3-mediated m6A modification of NUP210 may promote PCa metastasis and EMT. This newly identified METTL3/NUP210 axis deepens the understanding of PCa progression and suggests its potential for further therapeutic exploration.

查看原文本刊更多论文

METTL3通过介导NUP210 m6A修饰促进前列腺癌细胞转移和EMT。

背景：前列腺癌（PCa）是一种具有高转移潜力的年龄相关性上皮恶性肿瘤。尽管核孔蛋白210 （NUP210）与肿瘤进展有关，但其在前列腺癌转移中的作用和机制尚不清楚。方法：采用生物信息学分析(Gene Expression Omnibus （GEO)/The University of Alabama at Birmingham CANcer data analysis Portal （UALCAN）数据库）和实验验证（quantitative real-time PCR （qRT-PCR）和western blot）评估NUP210、甲基转移酶样3 （METTL3）、转移相关标志物和上皮间质转化（epithelial-mesenchymal transition， EMT）相关标志物的表达。通过功能分析（transwell，体内转移模型）和机制研究（甲基化RNA免疫沉淀（MeRIP）， RNA结合蛋白免疫沉淀（RIP）和mRNA稳定性分析）来阐明METTL3/NUP210轴。结果：NUP210和METTL3在前列腺癌组织和细胞中高表达。NUP210基因下调可显著抑制前列腺癌转移和EMT。动物实验表明，NUP210沉默可以抑制体内前列腺癌的肺转移。METTL3介导的n6 -甲基腺苷（m6A）修饰稳定了NUP210 mRNA，援救实验证实，NUP210过表达逆转了METTL3沉默对PCa细胞转移和EMT的抑制作用。结论：mettl3介导的m6A修饰NUP210可能促进前列腺癌转移和EMT的发生。这个新发现的METTL3/NUP210轴加深了对PCa进展的理解，并表明其具有进一步治疗探索的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.