Integration analysis of miRNA-mRNA expression exploring their potential roles in intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second common primary hepatic malignancy tumor. In this study, an integrative analysis of differentially expressed genes (DEGs) and miRNAs from the ICC onset and adjacent normal tissues were performed to explore the regulatory roles of miRNA-mRNA interaction. A total of 1018 DEGs and 39 miRNAs were likely involved in ICC pathogenesis, suggesting the changes in cell metabolism in ICC development. The built network indicated that 30 DEGs were regulated by 16 differentially expressed miRNA. The screened DEGs and miRNA together were probably considered the biomarkers of ICC, and their important roles in ICC pathogenesis remain to be elucidated. This study could provide a good basis to uncover the regulatory mechanism of miRNA and mRNAs in ICC pathogenesis.

Figure 1

Distribution of the sequencing reads for the samples of (A) ICC tissues and (B) adjacent normal tissues. The gene distribution in the reference genome (GRCh38.p12) was shown in blue.

Figure 2

Analysis of the mRNA expression pattern in ICC tissues. (A) PCA analysis of the samples of ICC tissues (ICCs) and the adjunct normal tissues (Nors). Two groups were differentiated by shadows. (B) Volcano plot of gene expression. The reference lines of − Log₁₀(adjusted P-value) and |Log₂(fold change)| were set as 2. The down-regulated and up-regulated DEGs were shown in blue and red. (C) Heatmap of the DEGs. All samples were clustered into two groups (ICCs and Nors).

Figure 3

Analyses of (A) GO Enrichment and (B) KEGG Pathway of DEGs in ICC tissues. The down-regulated (left panel) and Up-regulated DEGs (right panel) were analyzed for GO terms and KEGG pathways, respectively. GO terms were shown in green, red, and blue for different categories. The gray bars indicate enriched DEGs per the background genes of each GO term.

Figure 4

Analysis of the miRNA expression pattern in ICC tissues. (A) Percentage and (B) abundance of the aligned reads for the samples of ICC tissues (ICCs) and the adjunct normal tissues (Nors). (C) PCA analysis of the samples (ICCs and Nors), the groups were differentiated by shadows. (D) Volcano plot of miRNA expression. The reference lines of − Log₁₀(adjusted P value) and |Log₂(fold change)| were set as 1. The significantly down-regulated and up-regulated miRNA was shown in blue and red. (E) Heatmap of the differentially expressed miRNA. All samples were clustered into two groups (ICCs and Nors).

Figure 5

Target prediction for the differentially expressed miRNAs and function analysis. Target prediction for significantly (A) down-regulated and (B) up-regulated miRNAs. The predicted genes surrounding the differentially expressed miRNA are shown in grey. The analyses of (C) GO Enrichment and (D) KEGG Pathway were performed with all (615) the predicted targets. The gray bars indicate enriched targets per the background genes of each GO term.

Figure 6

Integrative analysis of miRNA and DEGs expression profiling in ICC tissues. (A) Venn diagram of the DEGs and predicted targets. (B) Regulation network of the 30 screened DEGs with the relevant miRNAs. The down-regulation and the up-regulation of DEGs and miRNAs were shown in blue and red, respectively. (C) String analysis (string-db.org, Version 11.5) for protein–protein interaction of the 30 screened DEGs.