Background: To investigate the prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) and to construct a prognostic risk and immune activity model. Methods: We obtained clinical and RNA-seq information on OSCC patient data in The Cancer Genome Atlas (TCGA) Genome Data Sharing (GDC) portal. Through a combination of a differential analysis, Pearson correlation analysis and Cox regression analysis, ferroptosis-related lncRNAs were identified, and a prognostic model was established based on these ferroptosis-related lncRNAs. The accuracy of the model was evaluated via analyses based on survival curves, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA). Univariate Cox and multivariate Cox regression analyses were performed to evaluate independent prognostic factors. Then, the infiltration and functional enrichment of immune cells in high- and low-risk groups were compared. Finally, certain small-molecule drugs that potentially target OSCC were predicted via use of the L1000FWD database. Results: The prognostic model included 8 ferroptosis-related lncRNAs (FIRRE, LINC01305, AC099850.3, AL512274.1, AC090246.1, MIAT, AC079921.2 and LINC00524). The area under the ROC curve (AUC) was 0.726. The DCA revealed that the risk score based on the prognostic model was a better prognostic indicator than other clinical indicators. The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for OSCC. There were differences in immune cell infiltration, immune functions, m6A-related gene expression levels, and signal pathway enrichment between the high- and low-risk groups. Subsequently, several small-molecule drugs were predicted for use against differentially expressed ferroptosis-related genes in OSCC. Conclusions: We constructed a new prognostic model of OSCC based on ferroptosis-related lncRNAs. The model is valuable for prognostic prediction and immune evaluation, laying a foundation for the study of ferroptosis-related lncRNAs in OSCC.

Tyroservatide (YSV), a bioactive tripeptide, holds potential as an anti-tumor agent. However, its specific effects on oral squamous cell carcinoma (OSCC) have not been elucidated. This study aims to investigate the inhibitory effects of YSV on OSCC and explore the underlying molecular mechanisms. A series of in vitro experiments were conducted to assess the impact of YSV on OSCC cell viability, colony formation, cell cycle, and apoptosis. RNA sequencing (RNA-seq), molecular docking, and western blotting were employed to investigate the molecular mechanisms. Additionally, a subcutaneous tumor model was established to validate the in vitro findings. Furthermore, PI3K inhibitors LY294002 and PI3K-IN-1, were used to confirm the role of the PTEN/PI3K/AKT pathway in YSV-mediated OSCC inhibition. Cell cycle and apoptosis were analyzed to assess the combined effect of YSV and LY294002. YSV significantly inhibited OSCC proliferation by inducing cell cycle arrest and apoptosis. RNA-seq and molecular docking revealed that YSV regulated the PTEN/PI3K/AKT signaling pathway. Western blotting confirmed the modulation of this pathway both in vitro and in vivo. The use of PI3K inhibitors, LY294002 and PI3K-IN-1, further validated the involvement of the PTEN/PI3K/AKT pathway in YSV-induced anti-tumor effects. Notably, the combination of YSV and LY294002 synergistically enhanced cell cycle arrest and apoptosis, demonstrating effective anti-tumor activity. In vivo experiments also supported these findings. YSV inhibited the progression of OSCC by promoting cell cycle arrest and apoptosis through the regulation of the PTEN/PI3K/AKT signaling pathway. The combination of YSV and PI3K inhibitors, such as LY294002, exhibited enhanced anti-tumor activity, suggesting potential therapeutic strategies for OSCC treatment.

PurposePeriodontal ligament cells (PDLCs) play a significant role in orthodontic force induced bone remodeling. However, the molecular mechanisms by which PDLCs respond to mechanical stimuli and influence osteoclastic activities remain unclear. This study aims to investigate the role of UCHL1, a key deubiquitinating enzyme involved in protein degradation and cellular responses, in force-treated PDLCs during orthodontic tooth movement (OTM).Materials and MethodsIn this study, we conducted in vivo and in vitro experiments using human PDLCs and a rat model of OTM. Mechanical stress was applied to PDLCs, and UCHL1 expression was analyzed through quantitative real-time polymerase chain reaction (qPCR), Western blot, and immunofluorescence staining. UCHL1 knockdown was achieved using siRNA, and its effects on osteoclast differentiation were assessed. The role of the MAPK/ERK pathway was investigated using the MEK-specific inhibitor U0126. An animal model of OTM was established, and the impact of UCHL1 inhibitor-LDN57444 on OTM and osteoclastic activity was evaluated through micro-CT analysis, histological staining, and immunohistochemistry.ResultsMechanical force induced UCHL1 expression in PDLCs during OTM. UCHL1 knockdown downregulated the RANKL/OPG ratio in PDLCs, affecting osteoclast differentiation. LDN57444 inhibited OTM and osteoclastic activity. UCHL1 activation correlated with ERK1/2 phosphorylation in force-treated PDLCs.ConclusionsMechanical force mediated UCHL1 activation in PDLCs promotes osteoclast differentiation via the ERK1/2 signaling pathway during OTM.

We analyzed RNA-sequencing (RNA-seq) and clinical data from head and neck squamous cell carcinoma (HNSCC) patients in The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal to investigate the prognostic value of anoikis-related genes (ARGs) in HNSCC and develop new targeted drugs. Differentially expressed ARGs were screened using bioinformatics methods; subsequently, a prognostic model including three ARGs (CDKN2A, BIRC5, and PLAU) was constructed. Our results showed that the model-based risk score was a good prognostic indicator, and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database, the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database. Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno- and chemo-therapeutic responses. Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database. Finally, in vitro experiments were used to verify the database findings. The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results. BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells. Molecular docking, real-time PCR, cell counting kit-8 (CCK-8), plate clone, and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model, inhibit HNSCC cells survival rate, and promote anoikis in vitro. Therefore, we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC, paving the way for clinically targeting anoikis in HNSCC.

Mometasone furoate (MF) is a kind of glucocorticoid with extensive pharmacological actions, including inhibiting tumor progression; however, the role of MF in head and neck squamous cell carcinoma (HNSCC) is still unclear. This study aimed to evaluate the inhibitory effect of MF against HNSCC and investigate its underlying mechanisms. Cell viability, colony formation, cell cycle and cell apoptosis were analyzed to explore the effect of MF on HNSCC cells. A xenograft study model was used to investigate the effect of MF on HNSCC in vivo. The core targets of MF for HNSCC were identified using network pharmacology analysis, TCGA database analysis and real-time PCR. Molecular docking was performed to determine the binding energy. Protein tyrosine phosphatase non-receptor type 11 (PTPN11)-overexpressing cells were constructed, and then, the cell viability and the expression levels of proliferation- and apoptosis-related proteins were detected after treatment with MF to explore the role of PTPN11 in the inhibitory effect of MF against HNSCC. After cells were treated with MF, cell viability and the number of colonies were decreased, the cell cycle was arrested and cell apoptosis was increased. The xenograft study results showed that MF could inhibit cell proliferation via promoting cell apoptosis in vivo. PTPN11 was shown to be the core target of MF against HNSCC via network pharmacology analysis, TCGA database analysis and real-time PCR. The molecular docking results revealed that PTPN11 exhibited the strongest ability to bind to MF. Finally, MF could attenuate the effects of increased cell viability and decreased cell apoptosis caused by PTPN11 overexpression, suggesting that MF can inhibit the progression of HNSCC by regulating PTPN11. MF targeted PTPN11, promoting cell cycle arrest and cell apoptosis, and consequently exerting effective anti-tumor activity.

Aim: To investigate the role of Lipopolysaccharide (LPS) in the odontoclast differentiation of MDPC‐23 cells. It was hypothesized that MDPC‐23 odontoblast‐like cells may function as odontoclasts under the influence of LPS.Methodology: MDPC‐23 cells were cultured in the presence of 0.1 or 1 μg mL⁻¹ LPS for 6 days. Cell viability was determined using the CCK8 assay. TRAP staining, dentine resorption assay and ROS detection by confocal laser scanning microscope were used to test the odontoclast‐like function of the induced cells. In additional, the related protein expression was confirmed by Western blotting and ELISA. An unpaired Student's t‐test and one‐way anova were used in statistical analysis.Results: TRAP‐positive cells, which are multinucleated, on the dentine slice were significantly increased in 1 μg mL⁻¹ LPS‐induced cells (P < 0.05). Osteoclast‐specific proteins such as TRAP cathepsin K and Rac1 were upregulated in the 1 μg mL⁻¹ LPS‐treated cells (P < 0.05), whilst the expression of marker proteins of the RANKL‐RANK signalling pathway (RANKL, RANK and TRAF6) in the induced cells was not significantly changed (P > 0.05). ROS production was observed in the 1 μg mL⁻¹ LPS treatment group (P < 0.05), but no significant differences were observed in the level of RANKL in the cell supernatant between the LPS‐treated group and the control group (P > 0.05).Conclusions: A known value of 1 μg mL⁻¹ LPS might induce odontoblast‐like MDPC‐23 cells to generate odontoclast‐like cells or to function as odontoclasts. The data might provide a new explanation for the precursors of odontoclasts and root resorption.