基于微小RNA表达谱的甲状腺髓样癌关键调节微小RNA筛选

Screening of key regulatory microRNAs in medullary thyroid carcinoma based on microRNA expression chips

目的通过生物信息学分析观察40例甲状腺髓样癌患者的癌组织与癌旁组织的微小RNA（miRNAs，miR）表达谱变化，从而寻找疾病相关的重点miRNAs及其靶基因。方法从Gene Expression Omnibus（GEO）中下载甲状腺髓样癌患者的基因表达数据表达芯片原始数据GSE40807。首先比较了两种样本的差异表达miRNA，利用数据库预测出差异表达miRNA的靶基因，随后分析了这些靶基因的功能及参与的代谢通路，并构建了靶基因之间的互作网络及靶基因与转录因子的调控网络。结果与正常甲状腺比较，在甲状腺髓样癌中，有21个miRNAs表达发生了显著变化，其中18个miRNAs表达上调和3个miRNAs下调。利用11个预测靶基因数据库得到336个miRNA-靶基因关系对，对这些靶基因进行STRING蛋白互作网络分析，得到230个节点和491个关系对。此外对这些靶基因进行TF预测和调控网络构建，得到7个转录因子、156个节点和300个关系树。结论通过生物信息方法系统分析了甲状腺髓样癌相关miRNA表达谱及相关靶基因，筛选到miR-124、miR-7和miR-129-5作为甲状腺髓样癌的相关调节因子。

Objective To find key miRNAs and their target genes in thyroid medullary carcinoma by studying the microRNAs （miRNAs） expression profiling of cancer and normal tissues. Methods The raw data of miRNA expression profiling （ GSE40807 ） were downloaded from Gene Expression Omnibus （GEO） database. Differentially expressed miRNAs were first compared between samples from the two groups, then the functions of these target genes and their metabolic pathways were analyzed. The interac- tion networks among these target genes and the regulatory networks between target genes and transcription factors were constructed. Results There were 21 miRNAs which were significantly varied in thyroid me- dullary carcinoma compared to normal thyroid. Among them, 18 miRNAs were up -regulated, and 3 miRNAs were down - regulated. A total of 336 miRNA and target gene pairs were obtained from 11 predic- ted target databases. STRING protein interaction network analysis of these target genes revealed 230 nodes and 491 relationship trees. In addition, we reported 7 transcription factors, 156 nodes and 300 relation trees by conducting TF prediction and regulation network construction for these target genes. Conclusion We systematically analyzed the miRNA expression profiling and related target genes in thyroid medullary carcinoma by bioinformatics methods and screened some relevant regulatory factors such as miR - 124, miR - 7 and miR - 129 - 5. This study will provide effect direction and foundation for further research.