Gao Ji, Li Hongyan, Liu Lei, Song Lide, Lv Yanting, Han Yuping
Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Lett. 2017 Dec;14(6):7297-7303. doi: 10.3892/ol.2017.7124. Epub 2017 Oct 3.
The aim of the present study was to investigate risk-related microRNAs (miRs) for bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression data downloaded from the Cancer Genome Atlas were utilized for survival analysis. Risk factor estimation was performed using Cox's proportional regression analysis. A microRNA-regulated target gene network was constructed and presented using Cytoscape. In addition, the Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, followed by protein-protein interaction (PPI) network analysis. Finally, the K-clique method was applied to analyze sub-pathways. A total of 16 significant microRNAs, including hsa-miR-3622a and hsa-miR-29a, were identified (P<0.05). Following Cox's proportional regression analysis, hsa-miR-29a was screened as a prognostic marker of BUC risk (P=0.0449). A regulation network of hsa-miR-29a comprising 417 target genes was constructed. These target genes were primarily enriched in GO terms, including collagen fibril organization, extracellular matrix (ECM) organization and pathways, such as focal adhesion (P<0.05). A PPI network including 197 genes and 510 interactions, was constructed. The top 21 genes in the network module were enriched in GO terms, including collagen fibril organization and pathways, such as ECM receptor interaction (P<0.05). Finally, 4 sub-pathways of cysteine and methionine metabolism, including paths 00270_4, 00270_1, 00270_2 and 00270_5, were obtained (P<0.01) and identified to be enriched through DNA (cytosine-5)-methyltransferase (, methionine adenosyltransferase 2α () and spermine synthase (). The identified microRNAs, particularly hsa-miR-29a and its 4 associated target genes and , may participate in the prognostic risk mechanism of BUC.
本研究的目的是探究与膀胱尿路上皮癌（BUC）预后相关的风险微小RNA（miR）。从癌症基因组图谱下载的临床和微小RNA表达数据用于生存分析。使用Cox比例回归分析进行风险因素估计。使用Cytoscape构建并呈现微小RNA调控的靶基因网络。此外，利用注释、可视化和综合发现数据库进行基因本体（GO）和京都基因与基因组百科全书通路富集分析，随后进行蛋白质-蛋白质相互作用（PPI）网络分析。最后，应用K-团方法分析子通路。共鉴定出16个显著的微小RNA，包括hsa-miR-3622a和hsa-miR-29a（P<0.05）。经过Cox比例回归分析，hsa-miR-29a被筛选为BUC风险的预后标志物（P=0.0449）。构建了一个包含417个靶基因的hsa-miR-29a调控网络。这些靶基因主要富集于GO术语，包括胶原纤维组织、细胞外基质（ECM）组织以及通路，如粘着斑（P<0.05）。构建了一个包含197个基因和510个相互作用的PPI网络。网络模块中的前21个基因富集于GO术语，包括胶原纤维组织以及通路，如ECM受体相互作用（P<0.05）。最后，获得了4条半胱氨酸和甲硫氨酸代谢的子通路，包括路径00270_4、00270_1、00270_2和00270_5（P<0.01），并确定它们通过DNA（胞嘧啶-5）-甲基转移酶、甲硫氨酸腺苷转移酶2α和精胺合酶富集。鉴定出的微小RNA，特别是hsa-miR-29a及其4个相关靶基因，可能参与BUC的预后风险机制。
