ORIGINAL RESEARCH article

Front. Oncol.

Sec. Breast Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1530269

Fusobacterium nucleatum Promotes Metastasis of Breast Cancer via the miR-21-3p/FOXO3 Axis

Provisionally accepted
yiping huangyiping huang1Zhongzhong GuoZhongzhong Guo2zhaoyou zengzhaoyou zeng2yingfeng zhangyingfeng zhang3ziwei ranziwei ran2guoqing luoguoqing luo2Sandi ShenSandi Shen2Chenyu ShangChenyu Shang4Yaqin LiuYaqin Liu2peng zhoupeng zhou2Peng MaPeng Ma2haibiao linhaibiao lin5*Yang LuYang Lu2*Dongdong LiuDongdong Liu4*
  • 1School of Public Health, Dali University, Dali, China
  • 2Qingyuan People's Hospital, Qingyuan, China
  • 3University of South China, Hengyang, Hunan Province, China
  • 4Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  • 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China

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Distant metastasis remains the leading cause of mortality among breast cancer patients. Fusobacterium nucleatum (F. nucleatum), a bacterium commonly found in tumors, has been under investigation to understand its impact on tumors and its potential mechanisms. This study reveals that while F. nucleatum infection does not promote the proliferation of breast cancer cells in vitro, it significantly enhances epithelial-to-mesenchymal transition (EMT) and cell migration. Mechanistically, miR-21-3p was identified as the most significantly altered miRNA following F. nucleatum infection. Knockdown of miR-21-3p was shown to markedly inhibit F. nucleatum-mediated EMT and breast cancer cell migration. Additionally, predictions from online databases and cell model validations indicated that FOXO3 is a downstream target of miR-21-3p. Silencing FOXO3 further facilitated F. nucleatum-induced cell migration. In conclusion, our findings suggest that F. nucleatum enhances EMT and promotes breast cancer cell migration through the miR-21-3p/FOXO3 signaling axis.

Keywords: breast cancer, Fusobacterium nucleatum, miR-21-3p, FOXO3, metastasis

Received: 12 Dec 2024; Accepted: 15 May 2025.

Copyright: © 2025 huang, Guo, zeng, zhang, ran, luo, Shen, Shang, Liu, zhou, Ma, lin, Lu and Liu. 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:
haibiao lin, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China
Yang Lu, Qingyuan People's Hospital, Qingyuan, China
Dongdong Liu, Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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