ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1604554
This article is part of the Research TopicBacterial Extracellular Vesicles and AMR: Friends or Foes? From Novel Therapeutic Approaches to the Etiopathogenic Mechanisms of InfectionsView all articles
Multiomics profiling reveals that P. gingivalis-induced extracellular vesicle reprogramming promotes immune evasion in colorectal cancer through autophagy-mediated STING degradation
Provisionally accepted
- Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
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Objective: While Porphyromonas gingivalis (P. gingivalis) infection is a recognized pathogenic factor in colorectal cancer (CRC) and extracellular vesicles (EVs) are key mediators within the tumor microenvironment, the molecular composition of lEVs (large extracellular vesicles) derived from P. gingivalis-infected cancer cells remains poorly characterized. This study aimed to comprehensively define the molecular cargo alterations in lEVs secreted by CRC cells in response to P. gingivalis infection. Methods: We employed an integrated multi-omics approach to analyze lEVs secreted by P. gingivalis-infected HCT116 colorectal cancer cells. miRNA sequencing and quantitative proteomics were performed to profile miRNA and protein expression, respectively. Bioinformatic analysis identified differentially expressed molecules. Mechanistic studies involving immunoblotting and autophagy inhibition were used to validate and explore key findings. Results: P. gingivalis infection induced significant cargo remodeling in HCT116-derived lEVs. miRNA sequencing identified a total of 223 miRNAs, among which 28 were differentially expressed. Notably, six novel miRNAs were specifically upregulated in lEVs from infected cells. Quantitative proteomics revealed 1165 significantly altered proteins. Strikingly, 982 proteins were downregulated, including the critical antitumor immune regulator STING (Stimulator of Interferon Genes). We further confirmed STING downregulation in infected HCT116 cells and demonstrated that P. gingivalis infection promotes STING degradation via autophagy, explaining its reduced incorporation into lEVs. Conclusion: Our integrated multi-omics analysis demonstrates that P. gingivalis infection profoundly remodels the molecular landscape of CRC cell-derived lEVs. The specific depletion of immune-stimulating factors, most notably STING, within lEVs suggests a novel mechanism by which this pathobiont may contribute to immune evasion and promote tumor progression in P. gingivalis-associated colorectal cancer.
Keywords: Porphyromonas gingivalis, colorectal cancer, STING, Proteome, miRNA
Received: 02 Apr 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Zhang, Zhang, Huang, Lu, Liu, Xu and Wen. 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:
Yuanzhi Xu, amyxyz01@hotmail.com
Fuping Wen, wenfuping@sibcb.ac.cn
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