甲状腺癌非编码RNA与mRNA差异表达谱及竞争性内源RNA调控网络分析
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张成瑶, Email: cczhangcy@163.com

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中国抗癌协会-肿瘤研究青年科学基金资助项目(CAYC18A49) ;重庆市科研院所绩效激励引导专项基金资助
项目(cstc2017jxjl130022)。


Analysis of differential expression profiles of non-coding RNAs and mRNAs and competing endogenous RNA regulatory network in thyroid cancer
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    摘要:

    目的:通过生物信息学方法分析甲状腺癌预后相关的非编码RNA与mRNA及信号通路。
    方法:从癌症基因组图谱(TCGA)数据库中下载568例甲状腺癌患者的临床信息及其组织样本的非编码RNA(lncRNA、miRNA)与mRNA数据,筛选出差异表达的非编码RNA与mRNA,对差异表达的mRNA进行功能富集分析与通路分析;构建lncRNA-miRNA-mRNA的竞争性内源RNA(ceRNA)调控网络;结合临床信息进行生存分析获取与甲状腺癌预后相关的非编码RNA与mRNA。
    结果:共筛选出差异表达的lncRNA 497个(上调93个,下调404个),miRNA 72个(上调5个,下调67个),mRNA 1 097个(上调233个,下调864个)。功能富集分析结果显示差异表达的mRNA主要参与单组织过程、单组织细胞过程、刺激反应等生物学过程,受体结合、分子功能调节、钙离子调节等细胞功能以及细胞、细胞膜、细胞外组件等细胞构成过程。通路分析结果显示差异表达的mRNA主要参与神经反应受体-配体相互作用、细胞因子-细胞因子受体相互作用、肿瘤转录失调等信号通路的调节。构建的lncRNA-miRNA-mRNA ceRNA互作网络中,有2个差异表达lncRNA(MIR181A2HG、OPCML-IT1),1个差异表达miRNA(miRNA-184)和2个差异表达mRNA(E2F1、SALL3)与甲状腺癌的总体生存期明显有关(均P<0.05)。
    结论:所筛选的非编码RNA与mRNA以及相关信号通路在甲状腺癌的预后密切相关,并为甲状腺癌发生、发展机制的研究提供了新的方向。

    Abstract:

    Objective: To analyze the non-coding RNAs and mRNAs as well as signaling pathways associated with the prognosis of thyroid cancer by bioinformatics approaches.
    Methods: The clinical information of 568 thyroid cancer patients along with the non-coding RNA (lncRNAs, miRNAs) and mRNA data of their tissue samples were downloaded from the Cancer Genome Atlas (TCGA) database, and differentially expressed non-coding RNAs and mRNAs were screened, and functional enrichment analysis and pathway analysis were performed on the differentially expressed mRNAs. The competing endogenous RNA (ceRNA) regulatory network of lncRNA-miRNA-mRNA was constructed; Survival analysis based on the clinical information was conducted for obtaining the non-coding RNAs and mRNAs associated with the prognosis of thyroid cancer. 
    Results: A total of 497 differentially expressed lncRNAs (93 up-regulated and 404 down-regulated), 72 differentially expressed miRNAs (5 up-regulated and 67 down-regulated) and 1 097 differentially expressed mRNAs (233 up-regulated and 864 down-regulated) were screened. Functional enrichment analysis showed that the differentially expressed mRNAs were mainly enriched in the biological processes such as single-organism process, single-organism cellular process and response to stimulus, the cell function such as receptor binding, molecular function regulator, calcium ion binding, and the molecular components of cells such as cellular component, membrane and extracellular region. Pathway enrichment analysis showed that the differentially expressed mRNAs were mainly enriched in pathways such as neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and transcriptional misregulation in cancer. In the constructed ceRNA regulatory network of lncRNA-miRNA-mRNA, there were two lncRNA (MIR181A2HG, OPCML-IT1), one miRNA (miRNA-184) and two mRNA (E2F1, SALL3) were significantly related to the overall survival rate (all P<0.05).
    Conclusion: The identified non-coding RNAs and mRNAs as well as signaling pathways may closely be related to the prognosis of thyroid cancer, which may also open a new avenue for studying the mechanism of the occurrence and development of thyroid cancer.

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汤喜, 张成瑶, 周晓红, 辇伟奇, 龚靖淋, 张玉莲, 周迎春, 李真华,.甲状腺癌非编码RNA与mRNA差异表达谱及竞争性内源RNA调控网络分析[J].中国普通外科杂志,2018,27(11):1409-1416.
DOI:10.7659/j. issn.1005-6947.2018.11.007

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  • 收稿日期:2018-08-02
  • 最后修改日期:2018-10-19
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  • 在线发布日期: 2018-11-25