ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1608574
This article is part of the Research TopicExploring the Breast Tumor Microenvironment: Association to Metastasis, Novel Risk Factors and Novel Treatments and Immunotherapies: Volume II.View all 7 articles
The m 6 A modification of LINC01133 suppresses ER + breast cancer progression by modulating IGF2BP2 protein stability via a ubiquitination-dependent mechanism
Provisionally accepted
- 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- 2Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China Anhui Provincial Hospital, Hefei, Anhui Province, China
- 3Division of life sciences and medicine, University of Science and Technology of China, Hefei, Anhui Province, China
- 4Department of Orthopaedics, the first affiliated hospital of university of science and technology of China, Hefei, China
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Background: Breast cancer is characterized by highly heterogenous, and is a representative model to understand how molecular features of tumor biology decide therapeutic strategy. LINC01133 exhibits opposing expressing patterns across different breast cancer subtypes, yet its roles and mechanisms in ER+ breast cancer remain a loaded question.Methods: The expression of LINC01133 was initially assessed utilizing a public dataset TCGA and subsequently validated within clinical samples through RT-qPCR and in situ hybridization (ISH). To determine the role of LINC01133, various assays including colony formation, transwell, 5-Ethynyl-2’-deoxyuridine (EdU) labeling, and mouse xenograft experiments were performed. Additionally, the RNA immunoprecipitation (RIP), the RNA pull-down, the mass spectrometry (MS), and RNA stability assays were conducted to elucidate its mechanisms.Results: LINC01133 was dramatically downregulated in ER+ breast cancer, which results in unfavorable prognosis. Functionally, LINC01133 inhibited migration and invasion in vitro and metastasis in vivo of ER+ breast cancer cells. Mechanistically, LINC01133 can directly interact with IGF2BP2 protein, promoting its ubiquitination and degradation. The downregulation of LINC01133 was mediated by m6A modification, catalyzed by METTL3 and recognized by YTHDF2, causing half-life reduction and accelerated degradation of LINC01133.Conclusion: Our findings revealed the downregulation of LINC01133 in ER+ breast cancer and made novel insight to the role of METTL3/YTHDF2/LINC01133/IGF2BP2 axis in ER+ breast cancer, which might provide novel perspective in the design and development of novel anticancer drugs.
Keywords: LINC01133, IGF2BP2, m 6 A, METTL3, Heterogenous
Received: 09 Apr 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Li, Shan, Lei, Gao, Hao, Yu and Pan. 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: Yueyin Pan, Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China Anhui Provincial Hospital, Hefei, 230001, Anhui Province, China
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