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鉴定一个潜在的功能性环状RNA-微小RNA-信使RNA调控网络,用于研究膀胱癌的发病机制并提供可能的生物标志物。

Identification of a potentially functional circRNA-miRNA-mRNA regulatory network for investigating pathogenesis and providing possible biomarkers of bladder cancer.

作者信息

Lu Hong-Cheng, Yao Jia-Qi, Yang Xiao, Han Jie, Wang Jing-Zi, Xu Kun, Zhou Rui, Yu Hao, Lv Qiang, Gu Min

机构信息

1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, 210029 Jiangsu China.

2Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, 210029 Jiangsu China.

出版信息

Cancer Cell Int. 2020 Jan 29;20:31. doi: 10.1186/s12935-020-1108-3. eCollection 2020.

DOI:10.1186/s12935-020-1108-3
PMID:32015691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6990554/
Abstract

BACKGROUND

Circular RNAs (circRNAs) have received considerable attention in human cancer research. However, many circRNAs remain to be detected. In our study, we determined novel circRNAs and investigated their effects on bladder cancer (BCa).

METHODS

Microarray dataset GSE92675 was downloaded from Gene Expression Omnibus (GEO). Then, we combined computational biology with quantitative real-time polymerase chain reaction (qRT-PCR) to select related circRNAs in BCa. The selected circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory subnetwork was determined by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.

RESULTS

The regulatory network constructed from the microarray dataset (GSE92675) contained 49 differentially expressed circRNAs (DECs). GO and KEGG analyses showed that the MAPK and PI3K-AKT signaling pathways were statistically significant. On the basis of qRT-PCR and the degree value calculated by the cytoHubba plugin of Cytoscape, hsa_circ_0011385 was finally confirmed. The subnetwork around hsa_circ_0011385 was constructed. In addition, we created a protein-protein interaction (PPI) network composed of 67 nodes and 274 edges after removing independent nodes. GO and KEGG analyses showed that hubgenes were involved in cell cycle activities. Moreover, they could be regulated by miRNAs and play an eventful role in BCa pathogenesis.

CONCLUSIONS

We proposed a novel circRNA-miRNA-mRNA network related to BCa pathogenesis. This network might be a new molecular biomarker and could be used to develop potential treatment strategies for BCa.

摘要

背景

环状RNA(circRNAs)在人类癌症研究中受到了广泛关注。然而,仍有许多circRNAs有待发现。在我们的研究中,我们鉴定了新型circRNAs,并研究了它们对膀胱癌(BCa)的影响。

方法

从基因表达综合数据库(GEO)下载微阵列数据集GSE92675。然后,我们将计算生物学与定量实时聚合酶链反应(qRT-PCR)相结合,以筛选BCa中相关的circRNAs。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析确定了所选的circRNA-微小RNA(miRNA)-信使RNA(mRNA)调控子网络。

结果

从微阵列数据集(GSE92675)构建的调控网络包含49个差异表达的circRNAs(DECs)。GO和KEGG分析表明,MAPK和PI3K-AKT信号通路具有统计学意义。基于qRT-PCR和Cytoscape的cytoHubba插件计算的度值,最终确认了hsa_circ_0011385。构建了围绕hsa_circ_0011385的子网络。此外,在去除独立节点后,我们创建了一个由67个节点和274条边组成的蛋白质-蛋白质相互作用(PPI)网络。GO和KEGG分析表明,hubgenes参与细胞周期活动。此外,它们可能受miRNAs调控,并在BCa发病机制中发挥重要作用。

结论

我们提出了一个与BCa发病机制相关的新型circRNA-miRNA-mRNA网络。该网络可能是一种新的分子生物标志物,可用于开发BCa的潜在治疗策略。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be18/6990554/080942c00b6e/12935_2020_1108_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be18/6990554/870757e8d80d/12935_2020_1108_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be18/6990554/685b0c3be92c/12935_2020_1108_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be18/6990554/136c5cb4499a/12935_2020_1108_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be18/6990554/593b6e4479e8/12935_2020_1108_Fig11_HTML.jpg
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