Huang Yiping, Guo Zhongzhong, Zeng Zhaoyou, Shang Chenyu, Zhang Yingfeng, Ran Ziwei, Luo Guoqing, Shen Sandi, Liu Yaqin, Zhou Peng, Ma Peng, Zhang Yanxia, Lin Haibiao, Lu Yang, Liu Dongdong
School of Public Health, Dali University, Dali, Yunnan, China.
Division of Gastroenterology, Institute of Digestive Disease, The Affiliated Qingyuan Hospital, Qingyuan People's Hospital, Guangzhou Medical University, Qingyuan, Guangdong, China.
Front Oncol. 2025 Jun 16;15:1530269. doi: 10.3389/fonc.2025.1530269. eCollection 2025.
This study aims to investigate the impact of Fusobacterium nucleatum (F. nucleatum) infection on distant metastasis in breast cancer and its underlying mechanisms.
Clinical breast cancer samples were collected, and F. nucleatum was identified through bacterial isolation and culture. In vitro and in vivo infection models were established using the isolated bacteria. The impact of F. nucleatum infection on breast cancer cell proliferation and migration was evaluated. High-throughput sequencing and bioinformatics analyses were performed to identify microRNAs exhibiting significant expression changes following F. nucleatum infection. Gene knockdown of miR-21-3p was utilized to assess its role in F. nucleatum-mediated epithelial-mesenchymal transition and cell migration. Online databases predicted the downstream targets of miR-21-3p, which were subsequently validated in cell models. Additionally, the effect of silencing FOXO3 on F. nucleatum-induced cell migration was examined.
Both in vitro and in vivo experiments showed that F. nucleatum infection did not affect cell proliferation but significantly enhanced EMT and migration. miR-21-3p was significantly upregulated after infection, and silencing it reduced F. nucleatum-induced migration. FOXO3 was identified as a downstream target of miR-21-3p, and silencing FOXO3 further enhanced cell migration.
F. nucleatum promotes breast cancer cell migration through the miR-21-3p/FOXO3 pathway. This study highlights the role of F. nucleatum in breast cancer metastasis and suggests potential therapeutic targets for intervention.
本研究旨在探讨具核梭杆菌（F. nucleatum）感染对乳腺癌远处转移的影响及其潜在机制。
收集临床乳腺癌样本，通过细菌分离培养鉴定F. nucleatum。使用分离出的细菌建立体外和体内感染模型。评估F. nucleatum感染对乳腺癌细胞增殖和迁移的影响。进行高通量测序和生物信息学分析，以鉴定F. nucleatum感染后表现出显著表达变化的微小RNA。利用miR-21-3p的基因敲低来评估其在F. nucleatum介导的上皮-间质转化和细胞迁移中的作用。在线数据库预测miR-21-3p的下游靶点，随后在细胞模型中进行验证。此外，还检测了沉默FOXO3对F. nucleatum诱导的细胞迁移的影响。
体外和体内实验均表明，F. nucleatum感染不影响细胞增殖，但显著增强上皮-间质转化和迁移。感染后miR-21-3p显著上调，沉默它可减少F. nucleatum诱导的迁移。FOXO3被鉴定为miR-21-3p的下游靶点，沉默FOXO3进一步增强细胞迁移。
F. nucleatum通过miR-21-3p/FOXO3途径促进乳腺癌细胞迁移。本研究突出了F. nucleatum在乳腺癌转移中的作用，并提出了潜在的干预治疗靶点。
