Fusobacterium nucleatum, an anaerobic oral opportunistic pathogen associated with periodontitis, has been considered to be associated with the development of oral squamous cell carcinoma (OSCC). However, the initial host molecular alterations induced by F. nucleatum infection which may promote predisposition to malignant transformation through epithelial–mesenchymal transition (EMT) have not yet been clarified. In the present study, we monitored the ability of F. nucleatum to induce EMT‐associated features, and our results showed that F. nucleatum infection promoted cell migration in either noncancerous human immortalized oral epithelial cells (HIOECs) or the two OSCC cell lines SCC‐9 and HSC‐4, but did not accelerate cell proliferation or cell cycle progression. Mesenchymal markers, including N‐cadherin, Vimentin, and SNAI1, were upregulated, while E‐cadherin was decreased and was observed to translocate to the cytoplasm. Furthermore, FadA adhesin and heat‐inactivated F. nucleatum were found to cause a similar effect as the viable bacterial cells. The upregulated lncRNA MIR4435‐2HG identified by the high‐throughput sequencing was demonstrated to negatively regulate the expression of miR‐296‐5p, which was downregulated in F. nucleatum‐infected HIOECs and SCC‐9 cells. The binding of MIR4435‐2HG and miR‐296‐5p was validated via a dual‐luciferase reporter assay. Additionally, knockdown of MIR4435‐2HG with siRNA leads to a decrease in SNAI1 expression, while miR‐296‐5p could further negatively and indirectly regulate SNAI1 expression via Akt2. Therefore, our study demonstrated that F. nucleatum infection could trigger EMT via lncRNA MIR4435‐2HG/miR‐296‐5p/Akt2/SNAI1 signaling pathway, and EMT process may be a probable link between F. nucleatum infection and initiation of oral epithelial carcinomas.
2 December 2020 in Journal of Cellular and Molecular Medicine
Accumulating evidence links Fusobacterium nucleatum with tumorigenesis. Our previous study demonstrated that F. nucleatum infection can induce epithelial‐mesenchymal transition (EMT) in oral epithelial cells and elaborated a probable signal pathway involved in the induction of EMT. However, the comprehensive profiling and pathways of other candidate genes involved in F. nucleatum promoting malignant transformation remain largely elusive. Here, we analysed the transcriptome profile of HIOECs exposed to F. nucleatum infection. Totally, 3307 mRNAs (ǀLog2FCǀ >1.5) and 522 lncRNAs (ǀLog2FCǀ >1) were identified to be differentially expressed in F. nucleatum‐infected HIOECs compared with non‐infected HIOECs. GO and KEGG pathway analyses were performed to investigate the potential functions of the dysregulated genes. Tumour‐associated genes were integrated, and top 10 hub genes (FYN, RAF1, ATM, FOS, CREB, NCOA3, VEGFA, JAK2, CREM and ATF3) were identified by protein‐protein interaction (PPI) network, and Oncomine was used to validate hub genes' expression. LncRNA‐hub genes co‐expression network comprising 67 dysregulated lncRNAs were generated. Together, our study revealed the alteration of lncRNA and potential hub genes in oral epithelial cells in response to F. nucleatum infection, which may provide new insights into the shift of normal to malignant transformation initiated by oral bacterial infection.
Dietary patterns greatly affect periodontitis, a chronic inflammatory disease that compromises both dental and systemic health. According to the emerging evidence, periodontal risk is more strongly associated with the overall dietary quality, especially fiber density intake, than any one micronutrient. While the average intake in industrialized countries is only half of the recommended 30 g day−1, high-fiber diets such as the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH), and whole-food plant-based diets are consistently associated with a 20–40% lower periodontitis prevalence. Dietary fiber plays a central role in regulating immune responses, strengthening tissue barriers, improving metabolic homeostasis, and shaping a healthy microbiome through its microbial fermentation products: short-chain fatty acids (SCFAs). This makes it a biologically rational and clinical evidence-supported strategy for the prevention and management of periodontitis. Integrating high-fiber diet recommendations into routine periodontal care and public health policies could be a crucial step towards more comprehensive oral and systemic health management. This narrative review elaborates on the mechanistic, observational, and intervention data highlighting the role of dietary fiber, especially SCFAs, in periodontal health.
To evaluate the association of periodontal inflamed surface area (PISA) and pan-immune-inflammation value (PIV) on the hazard of peri-implant mucositis in