Zhang Shitao, Zhang Xiaoping, Fu Xueqi, Li Wannan, Xing Shu, Yang Yiling
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Lett. 2018 Aug;16(2):2391-2401. doi: 10.3892/ol.2018.8954. Epub 2018 Jun 12.
The aim of the present study was to identify common microRNAs (miRNAs) in ovarian cancer (OC) cells and their exosomes using microarray data (accession number GSE76449) available from the Gene Expression Omnibus database, including exosomal samples from 3 OC cell lines, 1 normal ovarian surface epithelial cell line and their original cell samples. Differentially-expressed miRNAs (DE-miRNAs) were identified using the Linear Models for Microarray data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2 database. The potential functions of the target genes of the DE-miRNAs were analyzed using the Database for Annotation, Visualization and Integrated Discovery tool. The association between crucial miRNAs and target genes, and their clinical associations, were validated using The Cancer Genome Atlas data. As a result, 12 upregulated and 12 downregulated DE-miRNAs were shared by the 3 OC cell lines compared with normal controls in the exosomal samples, while 5 upregulated and 65 downregulated DE-miRNAs were shared between the original cells. Among them, 9 downregulated DE-miRNAs were shared between exosomal and original cells. The target genes of 4 common DE-miRNAs between exosomal and original cells (miR-127-3p, miR-339-5p, miR-409-3p and miR-654-3p) were predicted. Functional enrichment analysis indicated that these target genes may be involved in the Wnt signaling pathway (miR-409-3p-CTBP1 and miR-339-5p-CHD8) and Proteoglycans in cancer (miR-127-3p-PPP1CA). The negative associations between these 3 miRNAs and target genes were confirmed by a Pearson's correlation analysis. miR-127 was negatively associated with tumor grade. In conclusion, our results describe a set of miRNAs involved in OC development, in exosomal and non-exosomal manners, by regulating their target genes. They may be potential targets for treatment of OC.
本研究的目的是利用基因表达综合数据库中可获得的微阵列数据（登录号GSE76449），鉴定卵巢癌细胞（OC）及其外泌体中的常见微小RNA（miRNA），该数据库包括来自3种OC细胞系、1种正常卵巢表面上皮细胞系及其原始细胞样本的外泌体样本。使用微阵列数据线性模型方法鉴定差异表达的miRNA（DE-miRNA），并使用miRWalk2数据库预测DE-miRNA的mRNA靶标。使用注释、可视化和综合发现数据库工具分析DE-miRNA靶标基因的潜在功能。使用癌症基因组图谱数据验证关键miRNA与靶标基因之间以及它们的临床关联。结果，与外泌体样本中的正常对照相比，3种OC细胞系共有12种上调和12种下调的DE-miRNA，而原始细胞之间共有5种上调和65种下调的DE-miRNA。其中，外泌体和原始细胞共有9种下调的DE-miRNA。预测了外泌体和原始细胞之间4种常见DE-miRNA（miR-127-3p、miR-339-5p、miR-409-3p和miR-654-3p）的靶标基因。功能富集分析表明，这些靶标基因可能参与Wnt信号通路（miR-409-3p-CTBP1和miR-339-5p-CHD8）和癌症中的蛋白聚糖（miR-127-3p-PPP1CA）。通过Pearson相关性分析证实了这3种miRNA与靶标基因之间的负相关。miR-127与肿瘤分级呈负相关。总之，我们的结果描述了一组通过调节其靶标基因以外泌体和非外泌体方式参与OC发展的miRNA。它们可能是OC治疗的潜在靶点。
