Metastasis and immune suppression account for the poor prognosis of oral squamous cell carcinoma (OSCC). YKT6 is a member of the soluble NSF attachment protein receptor (SNARE) family, and the effect of YKT6 in OSCC remains elusive. The purpose of this study was to explore promising prognostic and immune therapeutic candidate biomarkers for OSCC and to understand the expression pattern, prognostic value, immune effects, and biological functions of YKT6. Genes correlated with tumor metastasis and CD8 + T cell levels were identified by weighted gene coexpression network analysis (WGCNA). Next, YKT6 was analyzed through differential expression, prognostic and machine learning analyses. The molecular and immune characteristics of YKT6 were analyzed in independent cohorts, clinical specimens, and in vitro. In addition, we investigated the role of YKT6 at the pan-cancer level. The results suggested that the red module in WGCNA, as a hub module, was associated with lymph node (LN) metastasis and CD8 + T cell infiltration. Upregulation of YKT6 was found in OSCC and linked to adverse prognosis. A nomogram model containing YKT6 expression and tumor stage was constructed for clinical practice. The aggressive and immune-inhibitory phenotypes showed YKT6 overexpression, and the effect of YKT6 on OSCC cell invasion and metastasis in vitro was observed. Moreover, the low expression of YKT6 was correlated with high CD8 + T cell levels and potential immunotherapy response in OSCC. Similar results were found at the pan-cancer level. In total, YKT6 is a promising candidate biomarker for prognosis, molecular, and immune characteristics in OSCC.

Human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells (MSCs) derived from dental and craniofacial tissues that exhibit high potential for differentiation into osteoblasts. Recently, microRNAs (miRNAs) have been established to play important roles in MSC osteogenesis. In the current study, we report that miR-21 was down-regulated in osteogenically differentiated PDLSCs. Overexpression of miR-21 significantly inhibited osteogenesis of hPDLSC, whereas its inhibition demonstrated the opposite effects. Furthermore, SMAD family member 5 (Smad5) was predicted to be a downstream target of miR-21 and was shown to undergo up-regulation in PDLSCs induced toward osteogenesis. Moreover, Smad5 and Runx2, which are the critical transcription factors in osteogenic differentiation, were predicted to be targets of miR-21. Suppression of miR-21 expression increased the level of Smad5 in vitro and during in vivo transplantation experiments. Furthermore, suppression of Smad5 inhibited osteogenic differentiation and decreased the protein level of Runx2. Taken together, these results suggested that miR-21 be mechanistically implicated in the regulation of osteogenic differentiation of hPDLSCs by targeting Smad5.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. Patients with poorly differentiated OSCC often exhibit a poor prognosis. AUNIP (Aurora Kinase A and Ninein Interacting Protein), also known as AIBp, plays a key role in cell cycle and DNA damage repair. However, the function of AUNIP in OSCC remains elusive. The differentially expressed genes (DEGs) were obtained using R language. Receiver operating characteristic curve analysis was performed to identify diagnostic markers for OSCC. The effectiveness of AUNIP in diagnosing OSCC was evaluated by machine learning. AUNIP expression was analyzed in publicly available databases and clinical specimens. Bioinformatics analysis and in vitro experiments were conducted to explore biological functions and prognostic value of AUNIP in OSCC. The gene integration analysis revealed 90 upregulated DEGs. One candidate biomarker, AUNIP, for the diagnosis of OSCC was detected, and its expression gradually increased along with malignant differentiation of OSCC. Bioinformatics analysis demonstrated that AUNIP could be associated with tumor microenvironment, human papillomavirus infection, and cell cycle in OSCC. The suppression of AUNIP inhibited OSCC cell proliferation and resulted in G0/G1 phase arrest in OSCC cells. The survival analysis showed that AUNIP overexpression predicted poor prognosis of OSCC patients. AUNIP could serve as a candidate diagnostic and prognostic biomarker for OSCC and suppression of AUNIP may be a potential approach to preventing and treating OSCC. FUND: Taishan Scholars Project in Shandong Province (ts201511106) and the National Natural Science Foundation of China (Nos. 61603218).

Fusobacterium nucleatum(F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built anF. nucleatuminfectious model with human periodontal ligament stem cells (PDLSCs) and showed thatF. nucleatumcould inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. TheF. nucleatumadhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations ofF. nucleatuminfection. NFκB1 and NFκB2 upregulated after 3 h ofF. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects ofF. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms ofF. nucleatumand the host inflammatory response at the early stage ofF. nucleatuminfection.

Maresin1 (MaR1) is an endogenous pro-resolving lipid mediator produced from polyunsaturated fatty acids and is believed to have antioxidant and anti-inflammatory properties. The objective of this study was to estimate MaR1′s impact on type 2 diabetic osteoporosis (T2DOP) and its pharmacological mode of action. An in vitro high-glucose model of the osteoblast cell line MC3T3-E1 was constructed and stimulated with MaR1. Type 2 diabetic rats were used to establish in vivo models of calvarial defects and were treated in situ with MaR1. The results revealed that, aside from preventing mortality and promoting the osteogenic capacity of MC3T3-E1 cells, MaR1 increased nuclear factor erythroid-2 related factor 2 (NRF2) signaling as well as the activity of glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11) and caused the restraint of ferroptosis under hyperglycemic stimulation. However, the therapeutic impact of MaR1 was significantly diminished due to NRF2-siRNA interference and the ferroptosis activator Erastin. Meanwhile, these results were validated through in vivo experiments. These findings imply that MaR1 activated the NRF2 pathway in vivo and in vitro to alleviate high-glucose-induced ferroptosis greatly. More crucially, MaR1 might effectively reduce the risk of T2DOP.