Numerous studies have shown that long noncoding RNAs (LncRNAs) are involved in the development and immune escape of head and neck squamous-cell carcinoma (HNSCC). However, the specific regulatory mechanisms by which LINC01123 regulates HNSCC and its correlation with immunity remain unclear. Therefore, this study’s primary purpose was to explore the mechanisms by which LINC01123 regulates the immune escape and progression of HNSCC. This study confirmed that LINC01123 is competitively bound to miR-214-3p, and miR-214-3p specifically targets B7–H3. The effects of LINC01123, B7–H3, and miR-214-3p on tumor progression, CD8⁺T-cell-mediated immune response, and the tumorigenicity of HNSCC in vitro and in vivo were examined through the downregulation or upregulation of LINC01123, B7–H3, and miR-214-3p. Our results indicated that LINC01123 and B7–H3 were highly expressed in HNSCC and are associated with poor prognosis in patients. Notably, overexpression of LINC01123 or B7–H3 or downregulation of miR-214-3p inhibited the function of CD8⁺T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8⁺T cells and promote the progression of HNSCC by upregulating B7–H3.

Radioresistance imposes a great challenge in reducing tumor recurrence and improving the clinical prognosis of individuals having oral squamous cell carcinoma (OSCC). OSCC harbors a subpopulation of CD44(+) cells that exhibit cancer stem-like cell (CSC) characteristics are involved in malignant tumor phenotype and radioresistance. Nevertheless, the underlying molecular mechanisms in CD44( + )-OSCC remain unclear. The current investigation demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in CD44(+) cells and promotes CSCs phenotype. Using RNA-sequencing analysis, we further showed that Spalt-like transcription factor 4 (SALL4) is involved in the maintenance of CSCs properties. Furthermore, the overexpression of SALL4 in CD44( + )-OSCC cells caused radioresistance in vitro and in vivo. In contrast, silencing SALL4 sensitized OSCC cells to radiation therapy (RT). Mechanistically, we illustrated that SALL4 is a direct downstream transcriptional regulation target of METTL3, the transcription activation of SALL4 promotes the nuclear transport of β-catenin and the expression of downstream target genes after radiation therapy, there by activates the Wnt/β-catenin pathway, effectively enhancing the CSCs phenotype and causing radioresistance. Herein, this study indicates that the METTL3/SALL4 axis promotes the CSCs phenotype and resistance to radiation in OSCC via the Wnt/β-catenin signaling pathway, and provides a potential therapeutic target to eliminate radioresistant OSCC.

Objectives: In head and neck squamous cell carcinoma (HNSCC), the interaction between epithelial-mesenchymal transformation (EMT) and hypoxia has been confirmed, and corresponding treatment methods have been investigated. Few studies have examined its combined effects and its potential clinical use, however. As a result, we developed a new scoring system based on EMT and hypoxia.Methods: We combined 200 hypoxia-related genes with 1184 EMT-related genes and finally constructed a score risk model containing 14 characteristic factors named the comprehensive index of EMT and hypoxia (CIEH) by the Lasso-Cox regression and univariate Cox regression method, which is used to predict prognosis and to guide treatment planning in HNSCC patients. Furthermore, we examined HNSCC expression of CIEH-related genes using the human protein atlas database.Results: Based on survival analysis results, CIEH value had a high prognostic value in HNSCC patients, a high CIEH value carries a poor prognostic significance in HNSCC. It is noteworthy that the CIEH value was correlated with tumor immune infiltration. Moreover, the CIEH had significant differences in age, stage, N, laterality, and peripheral nerve invasion, and that the CIEH could be an independent prognostic factor.Conclusions: This study constructed a CIEH model containing 14 characteristic factors, including hypoxia-related genes and EMT genes, that may be able to serve as potential biomarkers for HNSCC. According to the 14 characteristic factors in the CIEH model, a diagnostic kit can be packaged in the future to evaluate the survival of patients before tumor surgery and guide the subsequent treatment plan.

Introduction: Developing cartilage constructs with injectability, appropriate matrix composition and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. Bone marrow derived mesenchymal stem cells (BMSCs) have chondrogenic potential. Current approaches to drive their chondrogenic differentiation require extensive cell manipulation ex vivo and using exogenous growth factors. However, preventing hypertrophic transition of BMSCs in vivo and maintaining persistent chondrogenesis remain bottlenecks in clinical application. This study aimed to develop completely biological, injectable constructs to generate cartilage by co-transplanting chondrocyte and BMSCs. Methods: We fabricated fragmented chondrocyte macroaggregate (cell bricks) and mixed them with platelet rich plasma (PRP); BMSCs were mixed into the above constructs, allowed to clot and then subcutaneously injected into nude mice. Gross morphology observation, histological and immunohistochemical assay, immunofluorescence assay, biochemical analysis and gene expression analysis were used to compare the properties of BMSC-cell bricks-PRP complex with BMSC in PRP or BMSC/chondrocytes in PRP. Results: The constructs of BMSCs-cell bricks-PRP that were subcutaneously injected resulted in persistent chondrogenesis with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. Conclusions: We concluded that cell bricks-enriched PRP clotting provides an autologous substance derived niche for chondrogenic differentiation of BMSCs in vivo, which suggests that such an injectable, completely biological system is a suitable stem cell carrier for micro-invasive cartilage repair.