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基于数据挖掘和生物信息学方法鉴定甲状腺乳头状癌中的关键微小RNA

Identification of key miRNAs in papillary thyroid carcinoma based on data mining and bioinformatics methods.

作者信息

Wang Jianguo, Wu Liping, Jin Yuxia, Li Suping, Liu Xiaodan

机构信息

Department of Prenatal Diagnostics, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China.

出版信息

Biomed Rep. 2020 Jan;12(1):11-16. doi: 10.3892/br.2019.1256. Epub 2019 Nov 21.

Abstract

MicroRNAs (miRNAs) are a class of short (approximately 22 nucleotides), non-coding and endogenous RNA molecules that play pivotal roles in the occurrence and development of cancer. The present study aimed to investigate key miRNAs involved in papillary thyroid carcinoma (PTC). Two independent datasets (GSE73182 and GSE113629) were obtained from the GEO database. The differentially expressed miRNAs (DEmiRNAs) between PTC tissues and normal thyroid tissues were analyzed by GEO2R with the Limma R package. Key miRNAs in PTC were identified by the VennDiagram R package. The targets of the key miRNAs were predicted by miRWalk and were functionally enriched by clusterProfiler R package. Five miRNAs including hsa-miR-146b-5p, hsa-miR-15a-5p, hsa-miR-21-5p, hsa-miR-221-3p and hsa-miR-222-3p were identified as key miRNAs in PTC. The expression levels of these key miRNAs were upregulated in PTC. This finding was also confirmed in the other dataset. Target prediction of miRNAs indicated that hsa-miR-146b-5p, hsa-miR-15a-5p, hsa-miR-21-5p, hsa-miR-221-3p and hsa-miR-222-3p exhibited 2, 41, 3, 14 and 8 target genes, respectively. Enrichment analysis indicated that these key miRNAs were mainly involved in nine biological processes, such as regulation of MAP kinase activity, JNK cascade signaling and regulation of protein serine/threonine kinase activity) and in 28 pathways, including the mitogen associated protein kinase, the sphingolipid, ErbB, Ras and the C-type lectin receptor signaling pathways. In conclusion, the present study identified several key miRNAs in PTC, which serve as potential targets for PTC diagnosis and treatment.

摘要

微小RNA(miRNA)是一类短(约22个核苷酸)的非编码内源性RNA分子,在癌症的发生和发展中起关键作用。本研究旨在调查参与甲状腺乳头状癌(PTC)的关键miRNA。从基因表达综合数据库(GEO数据库)获得了两个独立的数据集(GSE73182和GSE113629)。使用Limma R包通过GEO2R分析PTC组织和正常甲状腺组织之间差异表达的miRNA(DEmiRNA)。通过VennDiagram R包鉴定PTC中的关键miRNA。通过miRWalk预测关键miRNA的靶标,并通过clusterProfiler R包进行功能富集。包括hsa-miR-146b-5p、hsa-miR-15a-5p、hsa-miR-21-5p、hsa-miR-221-3p和hsa-miR-222-3p在内的5种miRNA被鉴定为PTC中的关键miRNA。这些关键miRNA的表达水平在PTC中上调。这一发现也在另一个数据集中得到证实。miRNA的靶标预测表明,hsa-miR-146b-5p、hsa-miR-15a-5p、hsa-miR-21-5p、hsa-miR-221-3p和hsa-miR-222-3p分别表现出2、41、3、14和8个靶基因。富集分析表明,这些关键miRNA主要参与九个生物学过程,如丝裂原活化蛋白激酶活性的调节、JNK级联信号传导和蛋白质丝氨酸/苏氨酸激酶活性的调节,以及28条信号通路,包括丝裂原相关蛋白激酶、鞘脂、表皮生长因子受体(ErbB)、Ras和C型凝集素受体信号通路。总之,本研究鉴定了PTC中的几种关键miRNA,它们可作为PTC诊断和治疗的潜在靶点。

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