Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 4:11:1026.
doi: 10.3389/fgene.2020.01026. eCollection 2020.

Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma

Peitao Zhou  1 , Guanglei Zheng  2 , Yalin Li  2 , Dehua Wu  1 , Yuhan Chen  1
Affiliations

Construction of a circRNA-miRNA-mRNA Network Related to Macrophage Infiltration in Hepatocellular Carcinoma

Peitao Zhou et al. Front Genet. .

Abstract

Immune cells in the tumor microenvironment play a crucial role in regulating tumor progression. The circular RNA (circRNA) regulatory network involved in immune cell infiltration in hepatocellular carcinoma (HCC) remains largely unknown. In this study, the "estimate the proportion of immune and cancer cells" (EPIC) application is used to evaluate the fractions of immune cells, cancer-associated fibroblasts, and endothelial cells in HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients with a high macrophage fraction have better overall survival, and macrophage fraction is an independent prognostic factor for HCC. Next, the common differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) between paired tumor and non-tumor tissues are screened out from the TCGA and/or GEO databases. Through spearman correlation analysis, the macrophage-related DEmRNAs are identified to construct a circRNA-miRNA-mRNA regulatory network, which includes 6 DEcircRNAs, 7 DEmiRNAs, and 45 DEmRNAs. Functional enrichment analysis reveals that these DEmRNAs are mainly involved in immune-related processes. Furthermore, six hub DEmRNAs are identified to establish a hub circRNA regulatory network. Among the DEmRNAs in the network, PRC1 is identified as the most influential node. PRC1 high expression is correlated with poor prognosis and low macrophage infiltration in HCC. Taken together, we identify a certain circRNA regulatory network related to macrophage infiltration and provide novel insight into the mechanism of study and therapeutic targets for HCC.

Keywords: circular RNA; hepatocellular carcinoma; macrophage; non-coding RNAs; regulatory network.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
The prognostic value of six cell fractions in HCC patients from TCGA. (A) The composition of six cell fractions in HCC patients (n = 343). (B) The OS analysis of HCC patients with top (n = 86) and bottom 25% (n = 85) infiltration level of six cell fractions.
FIGURE 2
FIGURE 2
The prognostic value of six cell fractions in HCC patients from GSE14520. (A) The composition of six cell fractions in HCC patients (n = 221). (B) The OS analysis of HCC patients with top (n = 55) and bottom 25% (n = 56) infiltration levels of six cell fractions.
FIGURE 3
FIGURE 3
The DEmRNAs, DEmiRNAs, and DEcircRNAs identified from paired tumor and adjacent non-tumor cases. (A) The DEmRNAs were screened out from TCGA and GSE14520. The DEmiRNAs were screened out from TCGA. (B) Identification of DEmRNA-related macrophages from TCGA and GSE14520. (C) The DEcircRNAs were screened out from three GEO data sets.
FIGURE 4
FIGURE 4
Construction of the circRNA-miRNA-mRNA network based on 45 DEmRNAs related to macrophages. The network was constructed after taking the intersection of DEcircRNA-DEmiRNA pairs and DEmiRNA-macrophage-related DEmRNA pairs. The red diamond, yellow rectangle, and light green ellipse indicate circRNA, miRNA, and mRNA, respectively.
FIGURE 5
FIGURE 5
Construction of the hub circRNA-miRNA-mRNA network. (A) PPI network analysis of 45 DEmRNAs related to macrophage. (B) Two subnetworks of PPI network analyzed by the MCODE plugin of cytoscape. (C) Construction of the circRNA-miRNA-mRNA network based on six hub DEmRNAs related to macrophages. (D) Construction of the circRNA-miRNA-mRNA network based on PRC1. PRC1 was identified as the most influential node by the IVI method. The red diamond, yellow rectangle, and light green ellipse indicate circRNA, miRNA, and mRNA, respectively.
FIGURE 6
FIGURE 6
The Kaplan–Meier survival analysis of six hub macrophage-related DEmRNAs in HCC cases from TCGA (A) and GSE14520 (B).
FIGURE 7
FIGURE 7
The macrophage fractions in HCC cases with different expression levels of PRC1 or DTL from TCGA (A) and GSE14520 (B).
See this image and copyright information in PMC

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R. L., Torre L. A., Jemal A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68 394–424. 10.3322/caac.21492 - DOI - PubMed
    1. Cai J., Qi Q., Qian X., Han J., Zhu X., Zhang Q., et al. (2019). The role of PD-1/PD-L1 axis and macrophage in the progression and treatment of cancer. J. Cancer Res. Clin. Oncol. 145 1377–1385. 10.1007/s00432-019-02879-2 - DOI - PMC - PubMed
    1. Cao M. Q., You A. B., Zhu X. D., Zhang W., Zhang Y. Y., Zhang S. Z., et al. (2018). miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a. J. Hematol. Oncol. 11:12. 10.1186/s13045-018-0555-y - DOI - PMC - PubMed
    1. Chen Y., Yuan B., Chen G., Zhang L., Zhuang Y., Niu H., et al. (2020). Circular RNA RSF1 promotes inflammatory and fibrotic phenotypes of irradiated hepatic stellate cell by modulating miR-146a-5p. J. Cell. Physiol. 10.1002/jcp.29483 Online ahead of print - DOI - PubMed
    1. Dou L., Shi X., He X., Gao Y. (2020). Macrophage phenotype and function in liver disorder. Front. Immunol. 10:3112. 10.3389/fimmu.2019.03112 - DOI - PMC - PubMed

LinkOut - more resources