Orthopaedic Medical Center, The 2nd Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of Gynecology and Obstetrics, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7617-7624. doi: 10.3892/mmr.2017.7506. Epub 2017 Sep 18.
The present study aimed to screen potential genes associated with conventional osteosarcoma (OS) and obtain further information on the pathogenesis of this disease. The microarray dataset GSE14359 was downloaded from the Gene Expression Omnibus. A total of 10 conventional OS samples and two non‑neoplastic primary osteoblast samples in the dataset were selected to identify the differentially expressed genes (DEGs) using the Linear Models for Microarray Data package. The potential functions of the DEGs were predicted using Gene Ontology (GO) and pathway enrichment analyses. Protein‑protein interaction (PPI) data were also obtained using the Search Tool for the Retrieval of Interacting Genes database, and the PPI network was visualized using Cytoscape. Module analysis was then performed using the Molecular Complex Detection module. Additionally, the potential microRNAs (miRNAs) for the upregulated DEGs in the most significant pathway were predicted using the miRDB database, and the regulatory network for the miRNAs‑DEGs was visualized in Cytoscape. In total, 317 upregulated and 670 downregulated DEGs were screened. Certain DEGs, including cyclin‑dependent kinase 1 (CDK1), mitotic arrest deficient 2 like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine‑protein kinase (BUB1), were significantly enriched in the cell cycle phase and oocyte meiosis pathway. DEGs, including replication factor C subunit 2 (RFC2), RFC3, RFC4 and RFC5, were significantly enriched in DNA replication and interacted with each other. RFC4 also interacted with other DEGs, including CDK1, MAD2L1, NDC80 kinetochore complex and BUB1. In addition, RFC4, RFC3 and RFC5 were targeted by miRNA (miR)‑802, miR‑224‑3p and miR‑522‑3p. The DEGs encoding RFC may be important for the development of conventional OS, and their expression may be regulated by a number of miRNAs, including miR‑802, miR‑224‑3p and miR‑522‑3p.
本研究旨在筛选与传统骨肉瘤(OS)相关的潜在基因,并进一步了解该病的发病机制。从基因表达综合数据库中下载微阵列数据集 GSE14359。使用线性模型进行微阵列数据分析软件包,从数据集内选择 10 例传统 OS 样本和 2 例非肿瘤性原发性成骨细胞样本,以鉴定差异表达基因(DEGs)。通过基因本体论(GO)和途径富集分析预测 DEGs 的潜在功能。还使用搜索工具检索相互作用基因数据库获取蛋白质-蛋白质相互作用(PPI)数据,并使用 Cytoscape 可视化 PPI 网络。然后使用分子复合物检测模块进行模块分析。此外,使用 miRDB 数据库预测最显著途径中上调 DEGs 的潜在 microRNAs(miRNAs),并在 Cytoscape 中可视化 miRNA-DEGs 的调控网络。总共筛选到 317 个上调和 670 个下调的 DEGs。某些 DEGs,包括细胞周期蛋白依赖性激酶 1(CDK1)、有丝分裂阻滞缺陷 2 样 1(MAD2L1)和 BUB1 有丝分裂检查点丝氨酸/苏氨酸蛋白激酶(BUB1),在细胞周期阶段和卵母细胞减数分裂途径中显著富集。DEGs,包括复制因子 C 亚基 2(RFC2)、RFC3、RFC4 和 RFC5,在 DNA 复制中显著富集,并相互作用。RFC4 还与其他 DEGs 相互作用,包括 CDK1、MAD2L1、NDC80 着丝粒复合物和 BUB1。此外,RFC4、RFC3 和 RFC5 是 miRNA(miR)-802、miR-224-3p 和 miR-522-3p 的靶标。编码 RFC 的 DEGs 可能对传统 OS 的发生发展具有重要意义,其表达可能受包括 miR-802、miR-224-3p 和 miR-522-3p 等多种 miRNA 的调控。