Overexpression of m7G writers METTL1 and BUD23 confers oncogenicity in kidney renal clear cell carcinoma

IF 5.2 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2025-07-18 DOI:10.1002/path.6453

Anni Su, Jessica Tieng, Xueying S Xu, Richard P Tan, Yuchen Feng, Justin J-L Wong

{"title":"Overexpression of m7G writers METTL1 and BUD23 confers oncogenicity in kidney renal clear cell carcinoma","authors":"Anni Su, Jessica Tieng, Xueying S Xu, Richard P Tan, Yuchen Feng, Justin J-L Wong","doi":"10.1002/path.6453","DOIUrl":null,"url":null,"abstract":"Emerging evidence shows that N7-methylguanosine (m7G) modification and its writers contribute to the development of diverse cancers. However, the role of m7G writers in kidney renal clear cell carcinoma (KIRC) remains unclear. In this study we show that the catalytic components of m7G writers, METTL1 and BUD23, are overexpressed in advanced KIRC and are associated with worse overall survival. Knockdown of METTL1 or BUD23 inhibited cell proliferation, colony formation, and migration in KIRC cell lines, indicating their oncogenic role in KIRC. Furthermore, we observed that METTL1 and BUD23 expression was negatively correlated with the expression of key tumor suppressor genes commonly dysregulated in KIRC. We observed METTL1-mediated m7G methylation in mRNAs expressed by these tumor suppressor genes, indicating that METTL1 may regulate these genes via m7G modification. Overall, our study highlights the oncogenic role of METTL1 and BUD23 in KIRC and their potential as prognostic biomarkers and therapeutic targets in KIRC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"267 1","pages":"1-9"},"PeriodicalIF":5.2000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/path.6453","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6453","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Emerging evidence shows that N7-methylguanosine (m⁷G) modification and its writers contribute to the development of diverse cancers. However, the role of m⁷G writers in kidney renal clear cell carcinoma (KIRC) remains unclear. In this study we show that the catalytic components of m⁷G writers, METTL1 and BUD23, are overexpressed in advanced KIRC and are associated with worse overall survival. Knockdown of METTL1 or BUD23 inhibited cell proliferation, colony formation, and migration in KIRC cell lines, indicating their oncogenic role in KIRC. Furthermore, we observed that METTL1 and BUD23 expression was negatively correlated with the expression of key tumor suppressor genes commonly dysregulated in KIRC. We observed METTL1-mediated m⁷G methylation in mRNAs expressed by these tumor suppressor genes, indicating that METTL1 may regulate these genes via m⁷G modification. Overall, our study highlights the oncogenic role of METTL1 and BUD23 in KIRC and their potential as prognostic biomarkers and therapeutic targets in KIRC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Abstract Image

查看原文本刊更多论文

m7G基因表达者METTL1和BUD23在肾透明细胞癌中过度表达具有致癌性

新出现的证据表明，n7 -甲基鸟苷（m7G）修饰及其作者与多种癌症的发展有关。然而，m7G基因在肾透明细胞癌（KIRC）中的作用尚不清楚。在这项研究中，我们发现m7G转录因子的催化成分METTL1和BUD23在晚期KIRC中过度表达，并与较差的总生存率相关。METTL1或BUD23的敲低抑制了KIRC细胞系的细胞增殖、集落形成和迁移，表明它们在KIRC中具有致癌作用。此外，我们观察到METTL1和BUD23的表达与KIRC中常见的关键抑癌基因的表达呈负相关。我们在这些肿瘤抑制基因表达的mrna中观察到METTL1介导的m7G甲基化，表明METTL1可能通过m7G修饰来调节这些基因。总的来说，我们的研究强调了METTL1和BUD23在KIRC中的致癌作用，以及它们作为KIRC预后生物标志物和治疗靶点的潜力。©2025作者。《病理学杂志》由约翰·威利出版；儿子有限公司代表大不列颠及爱尔兰病理学会。

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

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.