Pan Denghua, Lin Peng, Wen Dongyue, Wei Yunpeng, Mo Qiuyan, Liang Liang, Chen Gang, He Yun, Chen Junqiang, Yang Hong
Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Am J Transl Res. 2018 Aug 15;10(8):2264-2276. eCollection 2018.
The mechanism of microRNAs (miRNAs) in thyroid cancer is still unclear. We identified miRNAs with differential expression in thyroid cancer versus normal tissues.
Microarray datasets were obtained from the GEO and ArrayExpress databases, and from publications found via PubMed, EMBASE, and Web of Science. Differentially expressed miRNAs were identified using the limma package, and their targets predicted using miRWalk. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses were performed using these target genes to explore potential carcinogenic mechanisms. Correlations between target gene and miRNA expression levels were examined. Changes in target protein expression were confirmed using data from The Human Protein Atlas and the Cancer Genome Atlas.
We ultimately included five datasets, and further analyzed the four miRNAs that were down-regulated in at least four datasets (miR-7-2-3p, miR-138-5p, miR-144-5p, miR-486-5p). Predicted targets were enriched in GO terms including extracellular matrix organization, cell surface, and receptor binding, and in KEGG cancer pathways. PPI analysis identified 10 hub genes as key potential targets of these miRNAs. The expression levels of eight target genes were negatively correlated with those of their respective miRNAs. Furthermore, eight predicted target genes in cancer-related pathways showed up-regulated protein and mRNA expression in thyroid cancer.
Low miRNA expression in thyroid cancer might influence tumorigenesis via critical pathways. The genes identified here may act as a starting point for further investigation of the carcinogenic mechanisms of these miRNAs.
微小RNA（miRNA）在甲状腺癌中的作用机制尚不清楚。我们鉴定了甲状腺癌组织与正常组织中差异表达的miRNA。
从基因表达综合数据库（GEO）和ArrayExpress数据库以及通过PubMed、EMBASE和科学网检索到的出版物中获取微阵列数据集。使用limma软件包鉴定差异表达的miRNA，并使用miRWalk预测其靶标。利用这些靶基因进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）网络分析，以探索潜在的致癌机制。检测靶基因与miRNA表达水平之间的相关性。使用人类蛋白质图谱和癌症基因组图谱的数据确认靶蛋白表达的变化。
我们最终纳入了5个数据集，并进一步分析了在至少4个数据集中下调的4种miRNA（miR-7-2-3p、miR-138-5p、miR-144-5p、miR-486-5p）。预测的靶标在包括细胞外基质组织、细胞表面和受体结合等GO术语以及KEGG癌症通路中富集。PPI分析确定了10个枢纽基因作为这些miRNA的关键潜在靶标。8个靶基因的表达水平与其各自的miRNA呈负相关。此外，癌症相关通路中的8个预测靶基因在甲状腺癌中蛋白和mRNA表达上调。
甲状腺癌中miRNA表达降低可能通过关键途径影响肿瘤发生。本文鉴定的基因可能作为进一步研究这些miRNA致癌机制的起点。
