RESUMEN
OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.
Asunto(s)
Neoplasias Óseas , Medicamentos Herbarios Chinos , Ginsenósidos , Osteosarcoma , Humanos , Simulación del Acoplamiento Molecular , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológicoRESUMEN
Extracellular matrix protein 2 (ECM2), which regulates cell proliferation and differentiation, has recently been reported as a prognostic indicator for multiple cancers, but its value in lower grade glioma (LGG) remains unknown. In this study, LGG transcriptomic data of 503 cases in The Cancer Genome Atlas (TCGA) database and 403 cases in The Chinese Glioma Genome Atlas (CGGA) database were collected to analyze ECM2 expression patterns and the relationship with clinical characteristics, prognosis, enriched signaling pathways, and immune-related markers. In addition, a total of 12 laboratory samples were used for experimental validation. Wilcoxon or Kruskal-Wallis tests demonstrated highly expressed ECM2 in LGG was positively associated with malignant histological features and molecular features such as recurrent LGG and isocitrate dehydrogenase (IDH) wild-type. Also, Kaplan-Meier (KM) curves proved high ECM2 expression could predict shorter overall survival in LGG patients, as multivariate analysis and meta-analysis claimed ECM2 was a deleterious factor for LGG prognosis. In addition, the enrichment of immune-related pathways for ECM2, for instance JAK-STAT pathway, was obtained by Gene Set Enrichment Analysis (GSEA) analysis. Furthermore, positive relationships between ECM2 expression with immune cells infiltration and cancer-associated fibroblasts (CAFs), iconic markers (CD163), and immune checkpoints (CD274, encoding PD-L1) were proved by Pearson correlation analysis. Finally, laboratory experiments of RT-qPCR and immunohistochemistry showed high expression of ECM2, as well as CD163 and PD-L1 in LGG samples. This study identifies ECM2, for the first time, as a subtype marker and prognostic indicator for LGG. ECM2 could also provide a reliable guarantee for further personalized therapy, synergizing with tumor immunity, to break through the current limitations and thus reinvigorating immunotherapy for LGG. AVAILABILITY OF DATA AND MATERIALS: Raw data from all public databases involved in this study are stored in the online repository (chengMD2022/ECM2 (github.com)).
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Antígeno B7-H1 , Quinasas Janus , Pronóstico , Factores de Transcripción STAT , Transducción de Señal , Glioma/genética , Glioma/terapia , Inmunoterapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapiaRESUMEN
Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metilación , Pronóstico , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Microambiente Tumoral , Endodesoxirribonucleasas/metabolismoRESUMEN
HOXA4 is a novel oncogene that has been observed in many kinds of tumors, but its role during glioma carcinogenesis and its clinical significance in diagnosing and prognosis human glioma remains unknown. In the present study, the Chinese Glioma Atlas (CGGA)-RNA sequencing database, CGGA microarray, and The Cancer Genome Atlas (TCGA)-RNA seq data from 1674 glioma patients were obtained from online databases and analyzed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to detect changes in the expression level of HOXA4 and characterize the relationship between HOXA4 and the clinical characteristics and prognosis of patients with glioma. Gene set enrichment analysis (GSEA) was used to reveal how HOXA4 regulates tumor-related pathways. HOXA4 mRNA levels in glioma tissue were higher than those in adjacent brain tissue. HOXA4 expression was also closely related to the clinical and molecular characteristics of gliomas, such as tumor grade and isocitrate dehydrogenase (IDH) mutation. Functional enrichment analysis revealed that HOXA4 could regulate cancer-related signal pathways, such as Cell cycle, Cell adhesion molecules cams, and JAK/STAT signaling pathway. Results of in vitro experiments confirmed that knockdown of HOXA4 blocks the cell cycle pathway and inhibits the proliferation, invasion and chemotherapy resistance in gliomas. We concluded that HOXA4 was an independent risk factor for glioma and may have clinical diagnostic potential. Meanwhile, our findings revealed that HOXA4 could be used as a biomarker for glioma diagnosis and treatment.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/patología , Isocitrato Deshidrogenasa/genética , Mutación/genética , Oncogenes , Factores de Transcripción/genética , Proteínas de Homeodominio/genéticaRESUMEN
Despite the growing recognition of ITGB3BP as an essential feature of various cancers, the relationship between ITGB3BP and glioma remains unclear. The main aim of this study was to determine the prognostic and diagnostic value of ITGB3BP in glioma. RNA-Seq and microarray data from 2222 glioma patients were included, and we found that the expression level of ITGB3BP in glioma tissues was significantly higher than that in normal brain tissues. Moreover, ITGB3BP can be considered an independent risk factor for poor prognosis and has great predictive value for the prognosis of glioma. Gene Set Enrichment Analysis results showed that ITGB3BP contributes to the poor prognosis of glioma by activating tumour-related signalling pathways. Some small-molecule drugs were identified, such as hexestrol, which may specifically inhibit ITGB3BP and be useful in the treatment of glioma. The TIMER database analysis results revealed a correlation between the expression of ITGB3BP and the infiltration of various immune cells in glioma. Our findings provide the first evidence that the up-regulation of ITGB3BP correlates with poor prognosis in human glioma. Thus, ITGB3BP is a potential new biomarker that can be used for the clinical diagnosis and treatment of glioma.
Asunto(s)
Neoplasias Encefálicas , Glioma , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , Humanos , Proteínas Nucleares/genética , Transducción de Señal , Regulación hacia ArribaRESUMEN
In recent years, gut microbiota have been linked to prevention and treatment of human diseases. Mushrooms are a source of potentially useful prebiotics because they contain polysaccharides, terpenoids, and other bioactive compounds. In the present review, we have summarized the prebiotic effects of mushrooms on gut microbiota in the context of immunological, metabolic, neurological, and cancer-related diseases in the last five years. We propose that mushrooms can not only change the composition of gut microbiota, but also promote secretion of beneficial metabolites. In addition, we point to the effects of host mRNA expression in gut microbiota as a direction of further study. Overall, these provide a background for further studies on the mechanisms of regulation of gut microbiota by mushrooms.