RESUMEN
Osteoarthritis (OA) is the most common degenerative joint disease caused by osteoblastic lineage cells. However, a comprehensive molecular program for osteoblasts in human OA remains underdeveloped. The single-cell gene expression of osteoblasts and microRNA array data were from human. After processing the single-cell RNA sequencing (scRNA-seq) data, it was subjected to principal component analysis (PCA) and T-Stochastic neighbor embedding analysis (TSNE). Differential expression analysis was aimed to find marker genes. Gene-ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and Gene set enrichment analysis (GSEA) were applied to characterize the molecular function of osteoblasts with marker genes. Protein-protein interaction (PPI) networks and core module were established for marker genes by using the STRING database and Cytoscape software. All nodes in the core module were considered to be hub genes. Subsequently, we predicted the potential miRNA of hub genes through the miRWalk, miRDB and TargetScan database and experimentally verified the miRNA by GSE105027. Finally, miRNA-mRNA regulatory network was constructed using the Cytoscape software. We characterized the single-cell expression profiling of 4387 osteoblasts from normal and OA sample. The proportion of osteoblasts subpopulations changed dramatically in the OA, with 70.42% of the pre-osteoblasts. 117 marker genes were included and the results of GO analysis show that up-regulated marker genes enriched in collagen-containing extracellular matrix were highly expressed in the pre-osteoblasts cluster. Both KEGG and GSEA analyses results indicated that IL-17 and NOD-like receptor signaling pathways were enriched in down-regulated marker genes. We visualize the weight of marker genes and constructed the core module in PPI network. In potential mRNA-miRNA regulatory network, hsa-miR-449a and hsa-miR-218-5p may be involved in the development of OA. Our study found that alterations in osteoblasts state and cellular molecular function in the subchondral bone region may be involved in the pathogenesis of osteoarthritis.
Asunto(s)
MicroARNs , Osteoartritis , Biomarcadores , Biología Computacional/métodos , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Osteoartritis/genética , Osteoblastos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ARNRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is an urgent public health issue due to its poor prognosis and resistance to anti-cancer agents. However, the role of cuproptosis, a newly identified form cell death, in applications of HNSCC is still not a known. In this study, single-cell RNA sequencing data was used to explore cuproptosis-related gene expression in the tumour microenvironment. A prognostic model was constructed based on the cuproptosis-related lncRNA. Various methods were performed to predict the overall survival (OS) of different risk score patients and explore difference in enrichment function and pathways between the risk score patients. Finally, a series of immunogenomic landscape analyses were performed and evaluated the immune function, immune infiltration and sensitivity to chemotherapeutic agents. Cancer cell cluster expressed the essential cuproptosis-related gene. As the risk score increased of HNSCC patients, a significant decrease in survival status and time occurred for patients in the high-risk score patient. The AUC for predicting 1-, 3-, and 5-years OS were 0.679, 0.713 and 0.656, indicating that the model regarded as an independent prognostic signature in comparison with the clinical-pathological characteristics. As a results of GO, the immune function and immune infiltration of different risk score patients were assessed, revealing significant differences in T cell function and abundance of different types of T cells. Low-risk score patients are relatively insensitive to chemotherapy agents such as docetaxel and cisplatin, and easily resistant to immunotherapy. A cuproptosis-related lncRNA prognostic model was constructed to predict OS of HNSCC patients and provided the newly therapeutic strategies.