ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1529657
This article is part of the Research TopicRNA Methylation and Demethylation in Tumorigenesis and as Therapeutic TargetsView all 5 articles
METTL3-mediated SNHG1 m 6 A modification promotes proliferation and migration by transcriptional regulation of WDR74 in osteosarcoma
Provisionally accepted
Guanzhen Qiu1Yuxin Bao1Yuanzhuang Zhang1Yeqiu Xu1Tianhua Qiao1Chenghao Li1Hanjie Zhai1Zhenjun Chen1
Fu Ren2
Yong Wang1*- 1Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning Province, China
- 2Shenyang Medical College, Shenyang, Liaoning Province, China
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RNA methyltransferase-like 3 (METTL3) catalyzes N6-methyladenosine (m6A) modification, broadly affecting the metabolism of coding and noncoding RNAs (ncRNAs). However, its role in small nucleolar RNA host gene 1 (SNHG1)-mediated proliferation and migration in osteosarcoma (OS) remains unclear. In this study, we found that METTL3 was upregulated in OS tissues and cell lines, promoting OS cell proliferation and migration. Mechanistically, METTL3, with the assistance of RNA binding motif protein 15 (RBM15), enhanced m6A modification and stabilized SNHG1. SNHG1, in turn, promoted OS progression by activating its neighboring gene WD repeat domain 74 (WDR74) through EWS RNA binding protein 1 (EWSR1) recruitment. These findings reveal that METTL3-mediated m6A modification stabilizes SNHG1, which transcriptionally activates WDR74 and facilitates OS progression.
Keywords: METTL3, N6-Methyladenosine, SNHG1, WDR74, Osteosarcoma, proliferation/metastasis
Received: 17 Nov 2024; Accepted: 28 Apr 2025.
Copyright: © 2025 Qiu, Bao, Zhang, Xu, Qiao, Li, Zhai, Chen, Ren and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yong Wang, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning Province, China
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