黄琪峰 郑琳琳 张菁

摘要：目的  利用生物信息学技术预测人类miR-222的靶基因，并分析其可能参与甲状腺癌的生物学过程和信号通路。方法  通过TCGA数据库研究miR-222的表达与甲状腺癌的关系，然后TCGA中表达下调的基因和网站预测的miR-222靶基因进行取交集得到重叠基因，再进行生物信息学分析确定与甲状腺癌相关的关键miR-222靶基因和通路，最后通过GEPIA对靶基因进行表达验证以及miR-222和靶基因的相关性分析。结果  miR-222在甲状腺癌中表达上调，富集分析表明miR-222很有可能参与血管紧张素受体-配体结合的调节，其中一个可能的靶基因是AGTR1，其在甲状腺癌中表达下调，与miR-222的表达呈负相关。结论  上调的miR-222可能以AGTR1为靶标，从而调节甲状腺癌中血管紧张素受体-配体结合发挥作用。

关键词：甲状腺癌;miR-222;AGTR1;生物信息学

中图分类号：R736.1                                 文献标识码：A                                 DOI：10.3969/j.issn.1006-1959.2020.01.026

文章编号：1006-1959（2020）01-0085-04

Prediction of Key Target Genes of miR-222 in Thyroid Cancer and Analysis of Its Signal Pathway

HUANG Qi-feng1，ZHENG Lin-lin2，ZHANG Jing1

（Department of Pharmacy1，Department of Ultrasound2，Run Run Shaw Hospital，Zhejiang University School of Medicine，

Hangzhou 310016，Zhejiang，China）

Abstract：Objective  To predict the target genes of human miR-222 using bioinformatics technology， and analyze the biological processes and signal pathways that miR-222 may participate in. Methods  TCGA database was used to study the relationship between miR-222 expression and thyroid cancer， then the genes with down-regulated expression in TCGA and miR-222 target genes predicted by the website were intersected to obtain overlapping genes， and bioinformatics analysis was performed to determine the correlation with thyroid cancer the key miR-222 target genes and pathways， and finally the target genes were verified by GEPIA and the correlation analysis between miR-222 and target genes. Results  miR-222 expression was significantly up-regulated in thyroid cancer. Enrichment analysis showed that miR-222 is likely to be involved in the regulation of angiotensin receptor-ligand binding. One of the possible target genes is AGTR1， which is expressed in thyroid cancer.Down-regulation was significantly negatively correlated with miR-222 expression.Conclusion  The up-regulated miR-222 is likely to target AGTR1， which may play a role in regulating angiotensin receptor-ligand binding in thyroid cancer.

Key words：Thyroid cancer;miR-222;AGTR1;Bioinformatics

甲状腺癌（thyroid cancer）是最常见的内分泌性恶性肿瘤，发病率逐年升高，严重威胁着人类的生命健康[1]。甲状腺癌的发生发展受多种调控因子共同作用，其具体机制目前尚不明确，因此确定其具体的发病机制，发现敏感的生物标志物和创新治疗方法来提高甲状腺癌的临床诊断和治疗水平是紧迫且具有挑战性的课题。微小RNA（miRNA）是一类含量丰富的非编码RNA分子，大小为15～21个核苷酸，它通过与目标基因的3'非翻译区域互补结合从而使目标基因沉默。miRNA已经被证实对广泛的生物过程具有调节作用，如细胞增殖、凋亡、分化和细胞周期调节[2，3]。miRNA使癌症在临床诊断和治疗中取得了较大进展[4，5]。……