基于circRNA-miRNA-mRNA网络揭示circRNA在甲状腺乳头状癌中的作用

苗欣; 刘培发; 菅雁兵; 郗洪庆; 陈凛

doi:10.3969/j.issn.2095-5227.2021.06.012

基于circRNA-miRNA-mRNA网络揭示circRNA在甲状腺乳头状癌中的作用

Role of circRNA in papillary thyroid carcinoma revealed by circRNA-miRNA-mRNA network

摘要

摘要:
背景甲状腺乳头状癌(papillary thyroid carcinoma，PTC)是一种常见的内分泌肿瘤，越来越多证据表明circRNA与肿瘤的发展密切相关，但circRNA在PTC中的功能尚不清楚。
目的基于生物信息学方法，构建PTC患者circRNA-miRNA-mRNA网络，探索circRNA在PTC预后中的调控机制。
方法从基因表达综合数据库(Gene Expression Omnibus，GEO)获取PTC患者的circRNA数据，其中肿瘤组6例，对照组6例；miRNA数据中包含肿瘤组5例，对照组5例；mRNA数据中包含肿瘤组32例，对照组51例。分别筛选出差异表达的circRNA、miRNA和mRNA，从而构建circRNA-miRNA-mRNA调控网络；下载癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库中PTC患者的RNA-seq数据及临床病例资料，通过Kaplan-Meier分析筛选出与PTC患者预后相关的mRNA，进一步构建与PTC患者预后相关的circRNA-miRNA-mRNA调控网络。
结果根据GEO数据库中的测序数据集，对比肿瘤组与对照组，最终筛选出30个差异表达circRNA、10个差异表达miRNA以及12个差异表达mRNA，成功构建了PTC相关circRNA-miRNA-mRNA调控网络；通过TCGA数据库发现KIT、SFN、SPRY4这3个mRNA与PTC患者预后密切相关，从而建立PTC预后相关circRNA-miRNA-mRNA调控子网络，明确circRNA在PTC中的调控机制。
结论本研究为circRNA通过ceRNA机制影响PTC预后提供依据，并为PTC的治疗和预后判断提供理论基础和新见解。

Abstract:
Background Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine system. Growing evidences suggest that circular RNAs (circRNAs) are closely related to the development of tumors. However, few studies to date have assessed the function of circRNAs in PTC.
Objective To construct the circRNA-miRNA-mRNA network of papillary thyroid carcinoma (PTC) patients based on bioinformatics, and explore the regulatory mechanism of circRNA in the prognosis of PTC.
Methods The circRNAs, miRNAs and mRNAs of PTC patients were obtained from Gene Expression Omnibus (GEO) database. The tissue samples of patients were divided into tumor group (circRNA: 6 cases; miRNA: 5 cases; mRNA: 32 cases) and control group (circRNA: 6 cases; miRNA: 5 cases; mRNA: 51 cases), and the differentially expressed circRNAs, miRNAs and mRNAs were screened out respectively to construct circRNA-miRNA-mRNA regulatory network. The transcriptome data and clinicopathological data of PTC patients were downloaded from the Cancer Genome Atlas (TCGA) database, then the differentially expressed mRNAs related to the prognosis of PTC patients were screened by Kaplan-Meier analysis to further construct the circRNA-miRNA-mRNA regulatory network involved in the prognosis of PTC patients.
Results Totally 30 differentially expressed circRNAs, 10 differentially expressed miRNAs and 12 differentially expressed mRNAs were screened out based on the sequencing datasets in GEO database, and the PTC-related circRNA-miRNA-mRNA regulatory network was then successfully constructed. Through the TCGA database, we found that KIT, SFN and SPRY4 were closely related to the prognosis of PTC patients, and subsequently the circRNA-miRNA-mRNA regulatory subnetwork related to the prognosis of PTC was established to clarify the regulatory mechanism of circRNAs in PTC.
Conclusion This study provides references for circRNAs mediating the prognosis of PTC through the ceRNA mechanism, and also provides theoretical evidences and new insights for predicting prognosis and treatment of PTC.

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