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食管癌中 lncRNA、miRNA 和 mRNA 表达谱的差异分析及 lncRNA 的预后价值。

Differential Analysis of lncRNA, miRNA and mRNA Expression Profiles and the Prognostic Value of lncRNA in Esophageal Cancer.

机构信息

College of Life Sciences, Zhengzhou University, 100 Kexue Road, Zhengzhou, 450001, People's Republic of China.

Department of Pharmacology, School of Basic Medicine, Zhengzhou University, 100 Kexue Road, Zhengzhou, 450001, Henan, China.

出版信息

Pathol Oncol Res. 2020 Apr;26(2):1029-1039. doi: 10.1007/s12253-019-00655-8. Epub 2019 Apr 10.

Abstract

Integrative central axis of lncRNA-miRNA-mRNA plays pivotal roles in tumor development and progression. However, the regulatory role of lncRNA-miRNA-mRNA in esophageal cancer remains elusive. TCGA database was utilized to investigate the differential expression of lncRNA, miRNA and mRNA in esophageal cancer (ESCA) and normal esophageal tissues, and GEO database was used to further validate the expression profile of key genes. Differential lncRNAs in TCGA database were submitted to Starbase, and lncRNAs related to overall survival were analyzed using Kaplan-Meier and log-rank test. We found 145 lncRNAs, 112 miRNAs and 2000 protein coding mRNAs were differentially expressed in ESCA samples, which were tightly involved in chromosome segregation, extracellular matrix assembly by GO assay, and KEGG assay revealed the correlation of differentially expressed genes with cell cycle, apoptosis and cGMP-PKG signaling pathway. Furthermore, there were 291 nodes in ceRNA network, which consisted of 40 lncRNAs, 28 miRNAs and 233 mRNAs, and formed 677 relations. Furthermore, 6 of 10 lncRNAs in TCGA database were consistent with GEO database, and expressions of 10 mRNAs in TCGA database all exhibited the same tendency with GEO database. Notably, we found 8 lncRNAs (WDFY3-AS2, CASC8, UGDH-AS1, RAP2C-AS1, AC007128.1, AC016205.1, AC092803.2 and AC079949.2) were correlated with overall survival of the patients with ESCA. The key differentially expressed genes participate in the development and progression of ESCA, and thus the elucidation of functions of lncRNA-miRNA-mRNA will provide new novel therapeutic target for the patients with ESCA.

摘要

lncRNA-miRNA-mRNA 整合的中心轴在肿瘤的发生和发展中起着关键作用。然而,lncRNA-miRNA-mRNA 在食管癌中的调控作用仍不清楚。TCGA 数据库被用来研究食管癌(ESCA)和正常食管组织中 lncRNA、miRNA 和 mRNA 的差异表达,GEO 数据库被用来进一步验证关键基因的表达谱。TCGA 数据库中的差异 lncRNA 被提交到 Starbase,使用 Kaplan-Meier 和对数秩检验分析与总生存期相关的 lncRNA。我们发现,在 ESCA 样本中,有 145 个 lncRNA、112 个 miRNA 和 2000 个蛋白质编码 mRNA 差异表达,这些基因通过 GO 分析紧密参与染色体分离,细胞外基质组装,KEGG 分析显示差异表达基因与细胞周期、细胞凋亡和 cGMP-PKG 信号通路相关。此外,ceRNA 网络有 291 个节点,由 40 个 lncRNA、28 个 miRNA 和 233 个 mRNA 组成,形成 677 种关系。此外,TCGA 数据库中有 10 个 lncRNA 中的 6 个与 GEO 数据库一致,TCGA 数据库中有 10 个 mRNA 的表达与 GEO 数据库一致。值得注意的是,我们发现 8 个 lncRNA(WDFY3-AS2、CASC8、UGDH-AS1、RAP2C-AS1、AC007128.1、AC016205.1、AC092803.2 和 AC079949.2)与 ESCA 患者的总生存期相关。关键差异表达基因参与 ESCA 的发生和发展,因此阐明 lncRNA-miRNA-mRNA 的功能将为 ESCA 患者提供新的治疗靶点。

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