Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma

Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma
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DOI:
10.12659/msm.913881
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发表时间:
2019-04-20
影响因子:
3.1
通讯作者:
Li, Yang
Li, Yang
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Li-Xin;Wan, Chuan;Li, Yang

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在世界范围内,皮肤转移性黑色素瘤具有高发病率和死亡率的侵袭性过程。因此,对转移性黑色素瘤发病机制的了解越来越多,包括表观遗传修饰和竞争性内源性RNA(ceRNA)的作用越来越受到关注。本研究旨在利用生物信息学数据对转移性黑色素瘤中的长链非编码RNA(lncRNA)、microRNA(miRNA)和mRNA表达进行整合分析,以构建转移性黑色素瘤中的ceRNA网络,分析数据来自癌症基因组图谱(TCGA)、基因本体(GO)数据库和京都基因和基因组百科全书(KEGG)途径。有471例病例包括103例原发性实体瘤和368例转移性黑色素瘤,包括转录组测序数据(包括lncRNA和mRNA); 452例有miRNA测序数据,芯片数据分析鉴定出转移性黑色素瘤中差异表达的85 6种mRNAs、67种miRNAs和250种lncRNAs,其中25种miRNAs、18种lncRNAs,18种mRNA参与了ceRNA的形成。存活分析鉴定了7个差异表达的mRNA,5个差异表达的miRNA,(miRNA-29 c、miRNA-100、miR-142- 3 p、miR-150、miR-516 a-2)和六种差异表达的lncRNA,(AC068594.1,C7orf71,FAM41C,GPC 5-AS1,MUC19,LINC 00402)与转移性黑色素瘤患者的生存时间相关。生物信息学数据和综合分析鉴定了lncRNA,miRNA,和mRNA表达来构建转移性黑色素瘤中的ceRNA和患者存活网络。这些发现支持了进一步研究ceRNA调节转移性黑色素瘤的机制的必要性。
Worldwide, metastatic melanoma of the skin has an aggressive course with high morbidity and mortality. Therefore, an increased understanding of the pathogenesis of metastatic melanoma has gained increasing attention, including the role of epigenetic modification and competing endogenous RNA (ceRNA). This study aimed to used bioinformatics data to undertake an integrative analysis of long noncoding RNA (lncRNA), microRNA (miRNA) and mRNA expression to construct a ceRNA network in metastatic melanoma.Data from the Cancer Genome Atlas (TCGA), the Gene Ontology (GO) database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed. There were 471 cases that included 103 primary solid tumors and 368 cases of metastatic melanoma that included transcriptome sequencing data (including lncRNA and mRNA); 452 cases had miRNA sequencing data.Analysis of chip data identified 85 6 mRNAs, 67 miRNAs, and 250 lncRNAs that were differentially expressed in cases of metastatic melanoma, of which 25 miRNAs, 18 lncRNAs, and 18 mRNAs participated in the formation of ceRNAs. Survival analysis identified seven differentially expressed mRNAs, five differentially expressed miRNAs (miRNA-29c, miRNA-100, miR-142-3p, miR-150, miR-516a-2), and six differentially expressed lncRNAs (AC068594.1, C7orf71, FAM41C, GPC5-AS1, MUC19, LINC00402) that were correlated with survival time in patients with metastatic melanoma.Bioinformatics data and integrative analysis identified lncRNA, miRNA, and mRNA expression to construct a ceRNA and patient survival network in metastatic melanoma. These findings support the need for further studies on the mechanisms involved in the regulation of metastatic melanoma by ceRNAs.