期刊
AGING-US
卷 13, 期 12, 页码 16425-16444出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.203165
关键词
bioinformatics; drug treatment; osteosarcoma; bone science; prognosis
资金
- National Natural Science Foundation of China [No12072129]
Novel prognostic and therapeutic targets for osteosarcoma patients were identified through gene expression analysis, with CDK1 and topoisomerase II alpha mRNA levels found to correlate with patient prognosis. Computational techniques were used to screen for potential CDK1 inhibitor PHA-793887, which was shown to be effective in reducing viability and clonogenicity of osteosarcoma cells in vitro.
To identify novel prognostic and therapeutic targets for osteosarcoma patients, we compared the gene expression profiles of osteosarcoma and control tissues from the GSE42352 dataset in the Gene Expression Omnibus. Differentially expressed genes were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment and protein-protein interaction network analyses. Survival curve analyses indicated that osteosarcoma patients with lower mRNA levels of cyclin-dependent kinase 1 (CDK1) and topoisomerase II alpha had better prognoses. Various computer-aided techniques were used to identify potential CDK1 inhibitors for osteosarcoma patients, and PHA-793887 was predicted to be a safe drug with a high binding affinity for CDK1. In vitro, MTT and colony formation assays demonstrated that PHA-793887 reduced the viability and clonogenicity of osteosarcoma cells, while a scratch assay suggested that PHA-793887 impaired the migration of these cells. Flow cytometry experiments revealed that PHA-793887 dose-dependently induced apoptosis in osteosarcoma cells. Western blotting and enzyme-linked immunosorbent assays indicated that CDK1 expression in osteosarcoma cells declined with increasing PHA-793887 concentrations. These results suggest that PHA-793887 could be a promising new treatment for osteosarcoma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据