Construction of Potential miRNA–mRNA Regulatory Network in COPD Plasma by Bioinformatics Analysis

Figures & data

Table 1 Details for GEO COPD Data

Accession	Platform	Sample	Normal	COPD	Gene/microRNA
GSE24709	GPL9040	Blood	19	24	microRNA
GSE61741	GPL9040	Blood	94	47	microRNA
GSE31568	GPL9040	Blood	70	24	microRNA
GSE56768	GPL570	Blood	29	49	gene

Abbreviations: COPD, chronic obstructive pulmonary disease; GEO, Gene Expression Omnibus.

Figure 1 Flow chart of constructing the miRNA–mRNA regulatory network in COPD plasma.

Abbreviations: COPD, chronic obstructive pulmonary disease; miRNA, microRNA.

Figure 2 Identification of the candidate DEMs.

Notes: (A) GSE24709 dataset; (B) GSE61741 dataset; (C) GSE31568 dataset. (D) Venn diagram indicated intersection of DEMs in the three datasets GSE24709, GSE61741, and GSE31568; (E) LogFC heatmap of the candidate DEMs. The |LogFC|>1.5 and an adjusted P value <0.05 were set as the threshold to screen DEMs. Red represents upregulated DEMs, green represents downregulated DEMs, and black represents no significant changes. The numbers in the box represent the logFC values.

Abbreviations: COPD, chronic obstructive pulmonary disease; DEMs, differentially expressed microRNAs; FC, fold change.

Figure 3 Potential transcription factors of DEMs predicted by FunRich.

Notes: (A) Transcription factors of upregulated DEMs; (B) Transcription factors of downregulated DEMs.

Abbreviation: DEMs, differentially expressed microRNAs.

Table 2 Potential Target Genes of the Significantly Upregulated and Downregulated DEMs

Upregulated DEMs	Number	Downregulated DEMs	Number
hsa-mir-126-5p	119	hsa-mir-182-3p	40
hsa-mir-130b-5p	344	hsa-mir-492	45
hsa-mir-556-3p	54	hsa-mir-497-5p	461
hsa-mir-1246	44	Total	543
hsa-mir-1258	36
hsa-mir-1468-5p	17
Total	596

Abbreviations: DEMs, differentially expressed microRNAs; miRNA, microRNA.

Figure 4 Potential target genes of DEMs predicted by miRNet.

Notes: (A) The miRNA-target gene network for upregulated DEMs; (B) The miRNA-target gene network for downregulated DEMs.

Abbreviations: DEMs, differentially expressed microRNAs; miRNAs, microRNAs.

Figure 5 GO annotation analysis for the target genes of DEMs in the biological process, cellular component, and molecular function.

Notes: (A) Barplot; (B) Dotplot. An adjusted P < 0.05 was identified as significantly changed GOs. The x-axis shows the adjusted P value (A) and gene ratio (B) of each term, and y-axis shows the GO annotation terms.

Abbreviations: DEMs, differentially expressed microRNAs; GO, Gene Ontology.

Figure 6 KEGG pathway analysis for the target genes of DEMs.

Notes: (A) Barplot; (B) Dotplot. An adjusted P < 0.05 was identified as significantly changed pathways. The x-axis shows the adjusted P value (A) and gene ratio (B) of each term, and y-axis shows the KEGG pathway terms.

Abbreviations: DEMs, differentially expressed microRNAs; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Table 3 Top 10 Hub Genes of the Significantly Upregulated and Downregulated DEMs in the PPI Network Ranked by MCC

Upregulated DEMs		Downregulated DEMs
Gene Symbol	Score	Gene Symbol	Score
MYC	22,916	FBXW7	87,178,818,926
VEGFA	22,125	CUL3	87,178,299,448
MAPK8	18,605	BTRC	87,178,293,375
STAT5A	15,337	ZBTB16	87,178,292,663
FOXO3	14,769	ANAPC13	87,178,292,097
FOXO1	14,200	CDC34	87,178,292,085
IGF1	13,828	FBXL18	87,178,291,926
NR3C1	12,845	FBXL20	87,178,291,922
HSPA8	11,147	SMURF1	87,178,291,408
EP300	8381	UBE2V1	87,178,291,229

Abbreviations: DEMs, differentially expressed microRNAs; MCC, maximal clique centrality; miRNA, microRNA; PPI, protein-protein interaction.

Figure 7 Identification of the hub genes for DEMs in the PPI network.

Notes: (A) PPI network of the top 30 hub genes for upregulated DEMs; (B) PPI network of the top 30 hub genes for downregulated DEMs.

Abbreviations: DEMs, differentially expressed microRNAs; PPI, protein-protein interaction.

Figure 8 The miRNA-hub gene regulatory network.

Notes: Diamond represents genes, ellipse represents miRNAs. Red represents upregulated DEMs and hub genes; Green represents downregulated DEMs and hub genes.

Abbreviations: DEMs, differentially expressed microRNAs; miRNAs, microRNAs.

Figure 9 The mRNA expression of the top 12 hub genes was determined from the GSE56768 dataset.

Notes: (A) MYC; (B) VEGFA; (C) MAPK8; (D) STAT5A; (E) FOXO3; (F) FOXO1; (G) FBXW7; (H) CUL3; (I) BTRC; (J) ZBTB16; (K) ANAPC13; (L) CDC34.