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Fusobacterium nucleatum drives colorectal cancer progression through the circPTBP3/miR-760/PUM1 axis

Oncogene (2026)Cite this article

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Abstract

Circular RNAs (circRNAs) perform critical functions in cancer biology, commonly serving as microRNA (miRNA) sponges to modulate gene expression. Nevertheless, their participation in gut microbiota-driven colorectal cancer (CRC) has yet to be substantially investigated. Fusobacterium nucleatum (F. nucleatum), a well-recognized oncogenic bacterium in the human gut, has been implicated in CRC development, but the underlying mechanisms are not fully defined. In this study, we identified a novel circRNA, circPTBP3, which is the most significantly upregulated circRNA upon F. nucleatum infection, and is significantly upregulated in CRC tissues. CircPTBP3 is preferentially transcribed over its host gene PTBP3 in response to F. nucleatum through activation of the transcription factor ETS1. Functional assays demonstrated that circPTBP3 enhances CRC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, circPTBP3 acts as a molecular sponge for miR-760, thereby relieving its suppression of the downstream target gene PUM1. In clinical CRC specimens, circPTBP3 expression showed a positive correlation with F. nucleatum abundance, PUM1 expression, larger tumor sizes, advanced TNM stages, and a negative correlation with miR-760 levels. These findings establish for the first time that circPTBP3 functions as a pivotal mediator of F. nucleatum ‘s oncogenicity, and reveal a novel F. nucleatum–circPTBP3–miR-760–PUM1 regulatory axis that promotes CRC progression. CircPTBP3 may serve as a potential biomarker and therapeutic target in F. nucleatum–associated colorectal carcinogenesis.

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Fig. 1: CircPTBP3 is highly expressed in F. nucleatum-related CRC.
Fig. 2: CircPTBP3 is highly expressed in F. nucleatum-related CRC.
Fig. 3: CircPTBP3 affects the proliferation and apoptosis of CRC cells.
Fig. 4: CircPTBP3 serves as a sponge for miR-760 in CRC cells.
Fig. 5: MiR-760 suppresses CRC progression through targeting PUM1.
Fig. 6: ETS1 mediates F. nucleatum-induced upregulation of circPTBP3 expression.
Fig. 7: CircPTBP3 mediates F. nucleatum-promoted tumor growth in vivo.
Fig. 8: Schematic diagram of the proposed molecular mechanism of circPTBP3 involved in colorectal tumorigenesis regulated by Fusobacterium nucleatum.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the Department of Gastroenterology, Shanghai General Hospital and Shanghai Institute of Digestive Disease for providing support on research conditions in this study.

Funding

This work was financially supported by grants from the National Natural Science Foundation of China (Nos.82203500, Nos.82303215).

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  1. These authors contributed equally: Chunmin Li, Qianqian Liu.

Authors and Affiliations

  1. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Chunmin Li & Hangchang Shen

  2. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Qianqian Liu, Tianhui Zou, Linna Fu & Yingxuan Chen

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Contributions

Conception and design: CML, YXC. Development of methodology: CML, QQL, LNF. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): CML, QQL, THZ. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): CML, QQL. Writing, review, and/or revision of the manuscript: QQL, HCS, CML, LNF. Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): CML, YXC. Study supervision: LNF, THZ, YXC.

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Correspondence to Tianhui Zou or Linna Fu.

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Li, C., Liu, Q., Shen, H. et al. Fusobacterium nucleatum drives colorectal cancer progression through the circPTBP3/miR-760/PUM1 axis. Oncogene (2026). https://doi.org/10.1038/s41388-026-03746-4

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