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lncRNAs、miRNAs 和 mRNAs 在肾母细胞瘤中的竞争性内源性 RNA(ceRNA)调控网络。

Competitive endogenous RNA (ceRNA) regulation network of lncRNAs, miRNAs, and mRNAs in Wilms tumour.

机构信息

Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China.

First Clinical College of Guangzhou Medical University, Guangzhou, 510230, China.

出版信息

BMC Med Genomics. 2019 Dec 16;12(1):194. doi: 10.1186/s12920-019-0644-y.

DOI:10.1186/s12920-019-0644-y
PMID:31842887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6915924/
Abstract

BACKGROUND

Competitive endogenous RNAs (ceRNAs) have revealed a new mechanism of interaction between RNAs. However, an understanding of the ceRNA regulatory network in Wilms tumour (WT) remains limited.

METHODS

The expression profiles of mRNAs, miRNAs and lncRNAs in Wilms tumour samples and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. The EdgeR package was employed to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package were performed, and the lncRNA-miRNA-mRNA interaction ceRNA network was established in Cytoscape. Subsequently, the correlation between the ceRNA network and overall survival was analysed.

RESULTS

A total of 2037 lncRNAs, 154 miRNAs and 3609 mRNAs were identified as differentially expressed RNAs in Wilms tumour. Of those, 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in the ceRNA regulatory network. The results of Gene Ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes, and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were mainly enriched in pathways related to the cell cycle. The survival analysis results showed that 16 out of the 205 lncRNAs, 1 out of 26 miRNAs and 5 out of 143 mRNAs were associated with overall survival in Wilms tumour patients (P < 0.05).

CONCLUSIONS

CeRNA networks play an important role in Wilms tumour. This finding might provide effective, novel insights for further understanding the mechanisms underlying Wilms tumour.

摘要

背景

竞争性内源性 RNA(ceRNA)揭示了 RNA 之间相互作用的一种新机制。然而,人们对 Wilms 瘤(WT)中的 ceRNA 调控网络的理解仍然有限。

方法

从 Therapeutically Applicable Research to Generate Effective Treatment(TARGET)数据库中获取 WT 样本和正常样本的 mRNA、miRNA 和 lncRNA 的表达谱。使用 EdgeR 包识别差异表达的 lncRNA、miRNA 和 mRNA。通过 ClusterProfile R 包进行功能富集分析,并在 Cytoscape 中构建 lncRNA-miRNA-mRNA 相互作用 ceRNA 网络。随后,分析 ceRNA 网络与总生存期的相关性。

结果

在 Wilms 瘤中,共鉴定出 2037 个 lncRNA、154 个 miRNA 和 3609 个 mRNA 作为差异表达的 RNA。其中,205 个 lncRNA、26 个 miRNA 和 143 个 mRNA 被纳入 ceRNA 调控网络。基因本体论(GO)分析结果表明,差异表达基因(DEGs)主要富集于与机械刺激反应、转录因子复合物和转录因子活性(与 RNA 聚合酶 II 近端启动子序列特异性 DNA 结合相关)相关的术语。京都基因与基因组百科全书(KEGG)通路分析结果表明,DEGs 主要富集于与细胞周期相关的通路。生存分析结果表明,在 Wilms 瘤患者中,205 个 lncRNA 中有 16 个、26 个 miRNA 中有 1 个、143 个 mRNA 中有 5 个与总生存期相关(P<0.05)。

结论

ceRNA 网络在 Wilms 瘤中发挥重要作用。这一发现可能为进一步理解 Wilms 瘤的机制提供有效的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/b9c697179163/12920_2019_644_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/15f6fc9dfa33/12920_2019_644_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/b9c697179163/12920_2019_644_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/15f6fc9dfa33/12920_2019_644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/f0c941ca19e9/12920_2019_644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/ec96a1ea74fa/12920_2019_644_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/a3f713917385/12920_2019_644_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/1459adc16541/12920_2019_644_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/5636fb231979/12920_2019_644_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/6915924/b9c697179163/12920_2019_644_Fig7_HTML.jpg

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