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. 2025 Aug 12;52(1):821.
doi: 10.1007/s11033-025-10926-0.

The interactions of Fusobacterium nucleatum and Porphyromonas gingivalis with microRNAs: contributions to oral squamous cell carcinoma

Amin Khoshbayan  1   2 , Negar Narimisa  2 , Shabnam Razavi  3   4 , Aref Shariati  5 , Masoumeh Tavakoli-Yaraki  6 , Davood Darban-Sarokhalil  2 , Amirnader Emami Razavi  7
Affiliations

The interactions of Fusobacterium nucleatum and Porphyromonas gingivalis with microRNAs: contributions to oral squamous cell carcinoma

Amin Khoshbayan et al. Mol Biol Rep. .

Abstract

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer, with about one-third of patients facing life-threatening and recurrent cases. Certain pathobionts in the oral microbiome contribute to the rise of inflammation and are directly involved in carcinogenesis. Analysis of the microbial profiles in OSCC patients reveals significant differences compared to healthy individuals. This study investigates the microbial composition, microRNA (miRNA) expression, and their related genes for the first time in Iranian patients diagnosed with OSCC.

Methods: The relative presence of Fusobacterium nucleatum, Porphyromonas gingivalis, Fusobacterium periodonticum, and Prevotella intermedia was assessed in both tumor and adjacent normal tissues using Real-time PCR on 20 pairs of fresh-frozen OSCC samples. The expression levels of four miRNAs (miR-21, miR-31, miR-26a, and miR-29a) and five target genes were investigated. Eventually, any potential association between these bacteria's presence and miRNAs' expression was analyzed.

Results: P. gingivalis and F. nucleatum were significantly more abundant in tumor samples than in the control samples. However, the other two bacteria did not show significant differences between the tumor and control samples. The relative expression levels of both oncomiRs were significantly higher in tumors compared to control samples. The analysis indicates a significant association between the presence of F. nucleatum and miR-21 expression. Additionally, a significant association was identified between P. gingivalis and the expression of miR-31. In addition, LOXL2 was the only miRNA-related gene that showed a substantial increase in tumor tissue compared to the control.

Conclusion: There is a significant association between the presence of F. nucleatum and miR-21; a relationship has been reported in colorectal cancer and is now observed in OSCC, and the expression of miR-31 was significantly correlated with P. gingivalis. Further research is needed to explore the prevalence and potential mechanisms of pathobionts and miRNA expression in OSCC.

Keywords: Fusobacterium nucleatum; Porphyromonas gingivalis; miR-21; miR-31; OSCC; Oral squamous cell carcinoma.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The ethics committee of the Iran University of Medical Sciences approved this study. The reference number is IR.IUMS.FMD.REC.1402.064. All participants have signed a written informed consent form before their participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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