Exploring the Complex Interplay Between Oral Fusobacterium nucleatum Infection, Periodontitis, and Robust microRNA Induction Including Multiple Known Oncogenic miRNAs
- Publicada
- Servidor
- Preprints.org
- DOI
- 10.20944/preprints202410.0630.v1
Fusobacterium nucleatum (F. nucleatum, Fn), an oral commensal that can become pathogenic, is associated with periodontitis (PD), adverse pregnancy outcomes, and colorectal cancer (CRC). MicroRNAs (miRNAs) are conserved, non-coding RNAs that play a regulatory role in gene expression and are detected in microbial infections. The aim of this study was to characterize the global microRNA expression kinetics in the mandibles of C57BL/6J mice infected with F. nucleatum for 8 and 16 weeks, and to identify miRNAs as biomarkers of the PD process using high-throughput NanoString nCounter® miRNA panels. Mice were divided into four groups: 8 weeks of Fn infection, 16 weeks of Fn infection, and their respective sham infection. Fn-infected mice at both 8- and 16 weeks showed 100% bacterial colonization on the gingival surface, along with a significant increase in alveolar bone resorption (p<0.0001) and intravascular dissemination to heart, indicating its invasive potential. Out of 577 miRNAs analyzed, seven miRNAs (miR-361-5p, miR-99b-5p) were upregulated, and two miRNAs (miR-362-3p and miR-720) were downregulated in the 8-week Fn infection group. In the 16-week Fn infection group, seven miRNAs (miR-361-5p, miR-99b-5p) were upregulated miRNAs and 13 miRNAs (miR-323-3p, miR-488) were downregulated. Notably, miRNAs such as miR-205, miR-210, miR-199a-3p which were differentially expressed (DE) in the Fn-infected mice at 8 weeks and miR-28 at 16 weeks, have been previously reported in human periodontitis. The 13 miRNAs induced by F. nucleatum (miR-361-5p) are linked to multiple malignancies, including esophageal, gastric, pancreatic, and colorectal cancers. Additionally, the DE miR-126-5p in the 8-week infection group has been identified as a potential biomarker for patients with PD and cardiovascular disease. The results indicate that F. nucleatum acts as a potent oncomicrobe, inducing several miRNAs associated with PD and linking it to systemic comorbidities. Furthermore, the study revealed similar expressions between PD-associated miRNAs and nine CRC tumor-expressed miRNAs.