Background: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. Methods: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. Results: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. Conclusion: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

Purpose: Micro-arc oxidation (MAO) is a fast and effective method to prepare nanoporous coatings with high biological activity and bonding strength. Simple micro/nano-coatings cannot fully meet the requirements of osteogenesis. To further improve the biological activity of a titanium surface, we successfully added biological magnesium (Mg²⁺) to a coating by micro-arc oxidation and evaluated the optimal magnesium concentration in the electrolyte, biocompatibility, cell adhesion, proliferation, and osteogenesis in vitro. Methods: Nanoporous titanium coatings with different concentrations of magnesium were prepared by micro-arc oxidation and characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The Mg²⁺ release ability of the magnesium-incorporated nanoporous titanium coatings was determined by inductively coupled plasma emission spectrometry (ICP-OES). The cytotoxicity of the magnesium-incorporated nanoporous titanium coatings was detected with live/dead double-staining tests. A CCK-8 assay was employed to evaluate cell proliferation, and FITC-phalloidin was used to determine the structure of the cytoskeleton by staining β-actin. Alkaline phosphatase (ALP) activity was evaluated by alizarin red S (ARS) staining to determine the effect of the coatings on osteogenic differentiation in vitro. The mRNA expression of osteogenic differentiation-related markers was measured using qRT-PCR. Results: EDS analyses revealed the successful addition of magnesium to the microporous coatings. The best magnesium concentration of the electrolyte for preparing the new coating was determined. The results showed that the nano-coatings prepared using the electrolyte with 2 g/L magnesium acetate best promoted the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Conclusion: These results suggest that the new titanium metal coating with a dual effect of promoting bone morphology and supplying the biological ion Mg²⁺ can be beneficial for rapid osseointegration.

RNA-binding proteins (RBPs) play fundamental roles in cancer; however, we still lack knowledge about to what extent RBPs are dysregulated, as well as about perturbed signaling pathways in cancer. In this study, we integrated analysis of multidimensional data across >10,000 cancer patients and >1,000 cell lines. We identified a top candidate RBP: eukaryotic translation initiation factor 2 subunit beta (EIF2S2). EIF2S2 is highly expressed in tumors and is associated with malignant features as well as patient prognosis. Functional assays performed in cancer cells revealed that EIF2S2 promotes cancer cell proliferation, migration, and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanistic investigations further demonstrated that EIF2S2 promotes tumorigenesis and progression by directly binding to a long non-coding RNA, LINC01600, which physically interacts with the MYC protein and increases its stability. Interestingly, we revealed that the EIF2S2-LINC01600-MYC axis can activate the Wnt/β-catenin pathway by inhibiting the activity of FHIT-related enhancers and FHIT expression. Finally, EIF2S2 knockdown combined with oxaliplatin treatment could be a potential combination therapy in cancer. Our integrated analysis provided detailed knowledge of the function of the EIF2S2-LINC01600-MYC axis, which will facilitate the development of rational combination therapies for cancer.

The relationship between oral squamous cell carcinoma (OSCC) development and the microbiome has attracted increasing attention. The depth of invasion (DOI) is an important indicator of tumor progression, staging and prognosis, and the change in the oral microbiome based on the DOI is unclear. This report describes the use of metagenomic analyses to investigate the relationship between the oral microbiome and the DOI. Forty patients in different DOI categories were recruited; 10 healthy people served as the control group. Swab samples collected from the participants were subjected to metagenomic analyses, and the oral microbial communities and their functions were investigated. The abundances ofFusobacterium nucleatum,Capnocytophaga sputigena,Porphyromonas endodontalis, andGemella haemolysanswere significantly increased in the patients compared with the controls. The abundances of some bacteria exhibited a stage-related trend. The abundances ofP. endodontalis,Gemella morbillorumandG. haemolysansincreased with increasing DOI. In contrast, the abundances ofPrevotella melaninogenica, Haemophilus parainfluenzaeandNeisseria flavescensdecreased with increasing DOI. Based on receiver operating characteristic (ROC) curve analysis, eight species were found to have predictive value:Rothia mucilaginosa,P. melaninogenica,H. parainfluenzae, andN. flavescensin the healthy control group andP. endodontalis,G. morbillorum,G. haemolysansandFusobacterium periodonticumin the high DOI group. In the functional analysis, several metabolic pathways were decreased, whereas flagellar assembly and bacterial chemotaxis showed an increasing trend as the disease progressed. Biofilm formation, flagella, lipopolysaccharide (LPS) and other virulence factors exhibited staging-related changes. These pathogenic pathways and factors had a clear correlation with specific pathogens. In particular, when OSCC progressed to the late stage, microbial diversity and functional potential changed greatly.

Background: The microbiota is a critical component of the complex human microenvironment, impacting various physiological processes and disease development via the microbe–host interaction. In particular, the oral microbiota profoundly affects tumor development and progression. There is increasing evidence that oral microbiota is associated with the development of oral cancer, especially oral squamous cell carcinoma (OSCC).Methods: We comprehensively analyzed the oral microbiota in 133 OSCC samples worldwide. Subsequently, we evaluated the microbial compositions between OSCC patients and healthy people and their correlation with clinical parameters. The value of the oral microbiota as a diagnostic and prognostic biomarker was also determined.Results: This study found differences in critical oral microbiota between OSCC and normal controls. The most notable differences are present in p_Firmicutes, p_Actinobacteria, c_Fusobacteriia, o_Fusobacteriales, f_Fusobacteriaceae, and g_Fusobacterium. All six-level oral microorganisms were also associated with the clinical characteristics of OSCC, particularly with the clinical outcomes (survival time and status). We developed a predictive model based on this. We found that five different oral microorganisms have high confidence and can be used for clinical diagnosis and prognostic prediction, except for p_Actinobacteria.Conclusion: This study revealed that the intratumor oral microbiota of OSCC patients worldwide and the microbial signatures of OSCC patients possess similar properties in different regions, further refining the shortcomings of the current research field. We revealed that the oral microbiota could be used as a biomarker to reflect human health and disease progression status. This will provide new directions for tumor microbiome research. This means we can develop strategies through diet, probiotics, and antibiotics for cancer prevention and treatment.