Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships.
Screening the key microRNAs and transcription factors in prostate cancer based on microRNA functional synergistic relationships.
复制标题
基于microRNA功能协同关系筛选前列腺癌关键microRNA和转录因子
DOI：
10.1097/md.0000000000005679
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发表时间：
2017-01
期刊：
影响因子：
1.6
通讯作者：
Cui Y
中科院分区：
文献类型：
--
作者：
Feng F;Wu J;Gao Z;Yu S;Cui Y
摘要前列腺癌(PC)是一种常见的肿瘤，转移性前列腺癌仍是不治之症。本研究旨在筛选与PC相关的关键microRNAs(MiRNAs)和转录因子(TF)。MiRNA表达谱数据集(GSE45604)从Gene Expression Omnibus数据库下载，包括50例PC和10例正常标本。利用LIMMA软件包对差异表达的miRNAs(DEmiRNAs)进行筛选，根据共调控靶基因的数目构建DEmiRNA-DEmiRNA共调控网络。利用R中的ClusterProfiler软件包对共调控靶基因进行功能富集化分析，利用共享至少1个功能项的miRNA相互作用构建DEmiRNA-DEmiRNA功能协同网络(MFSN)。在转录调控元件数据库的基础上，利用DEmiRNAs共同调控的肿瘤相关转录因子构建了DEmiRNA-TF调控网络。共鉴定出66个DEmiRNAs，其中上调表达的miRNAs 7个，目的基因18,642个；下调表达的miRNAs 59个，目的基因130,694个。构建了DEmiRNA-DEmiRNA共调控网络，包括66个DEmiRNAs和2024个共调控关系。在MFSN中，hsa-miR-1184、hsa-miR-1207-5p和hsa-miR-24具有显著的功能协同关系。DEmiRNA-Tf网络包含6个上调的DEmiRNA，其中4个为hsa-miR-1184、hsa-miR-1207-5p、hsa-miR-182和hsa-miR-183。在这4个miRNAs的子网络中，PPARA和CREM是关键的调控因子。4个上调的miRNAs(hsa-miR-1207-5p、hsa-miR-1184、hsa-miR-182和hsa-miR-183)和2个转录因子(PPARA和CREM)被确定为PC进展中的关键调控因子。以上4种miRNAs可能通过靶向PPARA和CREM参与PC的进展。
Abstract Prostate cancer (PC) is a common neoplasm, and metastatic PC remains incurable. The study aims to screen key microRNAs (miRNAs) and transcription factors (TFs) involved in PC. The miRNA expression profile dataset (GSE45604) was downloaded from Gene Expression Omnibus database, including 50 PC and 10 normal specimens. Differentially expressed miRNAs (DEmiRNAs) were identified through limma package in R, and DEmiRNA–DEmiRNA co-regulation network was constructed based on the number of co-regulated target genes. Functional enrichment analysis of co-regulated target genes was performed using clusterProfiler package in R, and miRNA interactions sharing at least 1 functional term were used to construct a DEmiRNA–DEmiRNA functional synergistic network (MFSN). Based on Transcriptional Regulatory Element Database, cancer-related TFs which were co-regulated by DEmiRNAs were utilized to construct a DEmiRNA–TF regulation network. A total of 66 DEmiRNAs were identified, including 7 up-regulated miRNAs with 18,642 target genes and 59 down-regulated miRNAs with 130,694 target genes. Then, the DEmiRNA–DEmiRNA co-regulation network was constructed, including 66 DEmiRNAs and 2024 co-regulation relationships. In MFSN, hsa-miR-1184, hsa-miR-1207-5p, and hsa-miR-24 had significant functional synergistic relationships. The DEmiRNA–TF network contained 6 up-regulated DEmiRNAs and 4 of them were highlighted, as hsa-miR-1184, hsa-miR-1207-5p, hsa-miR-182, and hsa-miR-183. In subnetwork of the 4 miRNAs, peroxisome proliferative activated receptor, alpha (PPARA) and cyclic AMP-responsive element modulator (CREM) were the critical regulated TFs. Four up-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-1184, hsa-miR-182, and hsa-miR-183) and 2 TFs (PPARA and CREM) were identified as key regulators in PC progression. The above 4 miRNAs might participate in PC progression by targeting PPARA and CREM.