Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China.
Clinical College, Jilin University, Changchun, China.
Aging (Albany NY). 2021 Jun 21;13(12):16425-16444. doi: 10.18632/aging.203165.
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 () 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. , 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.
为了鉴定骨肉瘤患者的新的预后和治疗靶点,我们比较了基因表达综合数据库(GEO)中的 GSE42352 数据集骨肉瘤和对照组织的基因表达谱。差异表达基因进行了基因本体、京都基因与基因组百科全书、基因集富集和蛋白质-蛋白质相互作用网络分析。生存曲线分析表明,骨肉瘤患者中 CDKN1A(cyclin-dependent kinase 1)和 TOP2A(topoisomerase II alpha)mRNA 水平较低的患者预后较好。利用各种计算机辅助技术鉴定了潜在的骨肉瘤患者 CDK1 抑制剂,PHA-793887 被预测为一种与 CDK1 具有高结合亲和力的安全药物。MTT 和集落形成实验表明,PHA-793887 降低了骨肉瘤细胞的活力和克隆形成能力,划痕实验表明,PHA-793887 损伤了这些细胞的迁移能力。流式细胞术实验表明,PHA-793887 以剂量依赖的方式诱导骨肉瘤细胞凋亡。Western blot 和酶联免疫吸附实验表明,随着 PHA-793887 浓度的增加,骨肉瘤细胞中 CDK1 的表达下降。这些结果表明,PHA-793887 可能是一种有前途的骨肉瘤新治疗方法。