miR-182 在卵巢癌中的预后价值及潜在通路信号分析：基于基因表达综合数据库（GEO）和生物信息学分析的研究。
Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis.
机构信息
Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, Guangxi, China.
Department of Gynecology and obstetrics, Shangyu People's Hospital, Shangyu, Zhejiang, China.
出版信息
J Ovarian Res. 2019 Nov 8;12(1):106. doi: 10.1186/s13048-019-0580-7.
BACKGROUND
Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated.
METHODS
We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed.
RESULTS
A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC.
CONCLUSIONS
Our study suggests that miR-182 is essential for the biological progression of OC.
背景
卵巢癌（OC）是妇科癌症患者死亡的常见原因。微 RNA（miRNA）被认为在 OC 的肿瘤发生中具有重要作用。尽管 miRNA 在 OC 中得到广泛认可，但 has-miR-182-5p（miR-182）在 OC 中的作用仍未完全阐明。
方法
我们通过分析来自基因表达综合数据库（GEO）的公共数据集和文献综述来评估 miR-182 表达在 OC 中的意义。此外，我们从 GEO 下载了三个 OC 和正常卵巢组织（NOT）的 mRNA 数据集，GSE14407、GSE18520 和 GSE36668，以鉴定差异表达基因（DEGs）。然后使用 miRWALK3.0 预测 hsa-miR-182-5p（TG_miRNA-182-5p）的靶基因。随后，我们通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路富集分析对 OC 中的 DEGs 和预测的 miR-182 靶基因进行基因重叠分析。STRING 和 Cytoscape 用于构建蛋白质-蛋白质相互作用（PPI）网络，并分析关键基因的预后效应。
结果
我们对文献的综述发现 OC 中 miR-182 普遍上调。共鉴定出 268 个 DEGs，包括 OC 相关和 miR-182 相关的 DEGs，其中 133 个基因来自 PPI 网络。许多 DEGs 富集在细胞外基质组织、癌症途径、焦点粘附和 ECM-受体相互作用中。两个关键基因，MCM3 和 GINS2，与 OC 患者的总生存显著相关。此外，我们通过网络分析鉴定了可能参与 OC 的隐蔽 miR-182 相关基因，如 DCN、AKT3 和 TIMP2。这些基因在 OC 中的表达均下调且与 miR-182 呈负相关。
结论
我们的研究表明，miR-182 对 OC 的生物学进展至关重要。
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