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. 2021 Jan 3;13(1):1153-1175.
doi: 10.18632/aging.202254. Epub 2021 Jan 3.

Construction of an mRNA-miRNA-lncRNA network prognostic for triple-negative breast cancer

Yuan Huang  1 , Xiaowei Wang  2 , Yiran Zheng  3 , Wei Chen  4 , Yabing Zheng  1 , Guangliang Li  1 , Weiyang Lou  5 , Xiaojia Wang  1
Affiliations

Construction of an mRNA-miRNA-lncRNA network prognostic for triple-negative breast cancer

Yuan Huang et al. Aging (Albany NY). .

Abstract

The aim of this study was to establish a novel competing endogenous RNA (ceRNA) network able to predict prognosis in patients with triple-negative breast cancer (TNBC). Differential gene expression analysis was performed using the GEO2R tool. Enrichr and STRING were used to conduct protein-protein interaction and pathway enrichment analyses, respectively. Upstream lncRNAs and miRNAs were identified using miRNet and mirTarBase, respectively. Prognostic values, expression, and correlational relationships of mRNAs, lncRNAs, and miRNAs were examined using GEPIA, starBase, and Kaplan-Meier plotter. It total, 860 upregulated and 622 downregulated differentially expressed mRNAs were identified in TNBC. Ten overexpressed and two underexpressed hub genes were screened. Next, 10 key miRNAs upstream of these key hub genes were predicted, of which six upregulated miRNAs were significantly associated with poor prognosis and four downregulated miRNAs were associated with good prognosis in TNBC. NEAT1 and MAL2 were selected as key lncRNAs. An mRNA-miRNA-lncRNA network in TNBC was constructed. Thus, we successfully established a novel mRNA-miRNA-lncRNA regulatory network, each component of which is prognostic for TNBC.

Keywords: biomarker; competing endogenous RNA; prognosis; triple-negative breast cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Identified differentially expressed mRNAs (DE-mRNAs) among triple-negative breast cancer (TNBC) tissues, tissues of other types of breast cancer, and normal samples in two Gene Expression Omnibus data sets. (A) The volcano plots of DE-mRNAs in the GSE45827 and GSE65194 data sets. The x-axis stands for log2 (fold change) of gene expression, and y-axis represents log-transformed P value. The red dots and green dots indicate the significantly overexpressed and underexpressed genes, respectively. The black dots indicate genes with no significant differential expression. |log2FC| > 1 and P value < 0.05 were the cutoff criteria. (B) The intersection of upregulated DE-mRNAs. (C) The intersection of downregulated DE-mRNAs. a: TNBC compared with normal samples in GSE45827; b: TNBC compared with normal samples in GSE65194; c: TNBC compared with tissues of other subtypes of breast cancer in GSE45827; d: TNBC compared with tissues of other subtypes of breast cancer in GSE65194.
Figure 2
Figure 2
Functional enrichment analysis for key DE-mRNAs. The top 10 enriched molecular function (MF), cellular component (CC), biological process (BP), and KEGG pathways of the upregulated and downregulated significant DE-mRNAs.
Figure 3
Figure 3
The top 20 hub genes selected from the PPI networks. (A) The PPI network of the upregulated significant DE-mRNAs. (B) The PPI network of the downregulated significant DE-mRNAs. (C) The top 20 hub genes of the upregulated significant DE-mRNAs. (D) The 20 hub genes of the downregulated significant DE-mRNAs.
Figure 4
Figure 4
Screening of key genes in TNBC. Key genes were identified from the top 10 hub genes of the significant dysregulated DE-mRNAs by merging the prognosis and expression analyses using Kaplan Meier-plotter and GEPIA databases. Expression boxplots and survival curves (overall survival [OS]) of 12 key genes, including 10 upregulated hub genes (CDK1, CCNB1, CCNA2, CDC20, TOP2A, CCNB2, MAD2L1, BUB1, KIF11, and RRM2) and two downregulated hub genes (ESR1 and IGF1) in TNBC are presented.
Figure 5
Figure 5
The mRNA-miRNA network established by Cytoscape software.
Figure 6
Figure 6
The prognostic values of NEAT1 and MAL2 in TNBC determined by the Kaplan-Meier plotter. (A) The prognostic value (overall survival [OS]) of NEAT1 in TNBC. (B) The prognostic value (relapse-free survival [RFS]) of NEAT1 in TNBC. (C) The prognostic value (OS) of MAL2 in TNBC. (D) The prognostic value (RFS) of MAL2 in TNBC.
Figure 7
Figure 7
The mRNA-miRNA-lncRNA competing endogenous RNA (ceRNA) network related to the prognosis of TNBC.
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