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结直肠癌血液外泌体ceRNA网络的构建及生物信息学分析

Construction of ceRNA Network and Bioinformatics Analyses of Blood Exosomal From Colorectal Cancer

  • 摘要: 为构建结直肠癌(colorectal cancer, CRC)患者血液外泌体circRNA/lncRNA-miRNA-mRNA的竞争性内源RNA(competitive endogenous RNA, ceRNA)网络,预测差异表达基因(differentially expressed genes, DEGenes)之间的潜在调控机制,我们从exoRBase数据库下载健康人(Homo sapiens)及CRC患者血液外泌体中信使RNA(messenger RNA, mRNA)、长非编码RNA(long non-coding RNA, lncRNA)、环状RNA(circular RNA, circRNA)的基因数据,并进行差异筛选,共发现120个差异mRNAs, 52个差异lncRNAs和81个差异circRNAs。利用多个数据库预测与lncRNA、circRNA和mRNA结合的miRNA,进而成功构建lncRNA/circRNA-miRNA-mRNA的ceRNA网络。基因本体(gene ontology, GO)分析表明,ceRNA网络中的DEGenes主要涉及细胞高尔基体的生物学调控及结构维持、细胞黏附连接及酶的催化活性。京都基因与基因组百科全书(kyoto encyclopedia of gene and genomes, KEGG)分析共富集到14条信号通路,主要涉及志贺氏菌(Shigella)病和MAPK信号通路。因此,本研究成功构建了CRC患者血液外泌体ceRNA网络,为探究CRC的发病机制奠定了基础。

     

    Abstract: To construct a competitive endogenous RNA(ceRNA) network of circRNA/lncRNA-miRNA-mRNA in blood exosomes of patients with colorectal cancer(CRC), and predict the potential regulatory mechanisms between differentially expressed genes(DEGenes), the data of messenger RNA(mRNA), long non-coding RNA(lncRNA), circular RNA(circRNA) from the blood of healthy volunteers and CRC patients were downloaded from the exoRBase database. After screening and analyses, a total of 120 mRNAs, 52 lncRNAs and 81 circRNAs were found to be differentially expressed in CRC patients. Multiple databases were used to predict miRNAs that can bind to lncRNA, circRNA and mRNA, and then the ceRNA network of lncRNA/circRNA-miRNA-mRNA was successfully constructed. Gene ontology(GO) analysis showed that DEGenes in the ceRNA network are mainly involved in the biological regulation and structure maintenance of the Golgi apparatus, cell adhesion and connection, and enzyme catalytic activity. The Kyoto Encyclopedia of Gene and Genomes(KEGG) analysis enriched 14 signaling pathways, mainly involved in shigellosis and MAPK signaling pathways. Therefore, this study successfully constructed the ceRNA network of blood exosomes in CRC patients, laying a foundation for exploring the pathogenesis of CRC patients.

     

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