Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

作者：Yuhan Chen, Yalin Li, Guanglei Zheng, Peitao Zhou · 发表于：PeerJ · 年份：2020 · DOI：10.7717/peerj.10198 · 被引用次数：32 · 研究领域：Circular RNAs in diseases、Ferroptosis and cancer prognosis、Immune cells in cancer

BACKGROUND: Macrophage play a crucial role in regulating tumor progression. This study intended to investigate the circular RNA (circRNA) regulatory network associated with macrophage infiltration in hepatocellular carcinoma (HCC). METHODS: The immune cell fractions of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium were calculated by Estimation of the Proportion of Immune and Cancer cells algorithm. The differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) were identified from HCC and adjacent non-tumor cases of TCGA or Gene Expression Omnibus database. The DEmRNAs related to macrophage were selected by weighted gene co-expression network analysis and then utilized to generate the circRNA-miRNA-mRNA network. A hub circRNA regulatory network was established based on the co-expressed DEmiRNAs and DEmRNAs owning contrary correlation with the clinical characteristics, survival and macrophage infiltration level. A gene signature based on the DEmRNAs in hub network was also generated for further evaluation. The circRNA binding bite for miRNA was detected by luciferase assay. RESULTS: High macrophage fraction predicted good survival for HCC. A circRNA-miRNA-mRNA network was constructed by 27 macrophage related DEmRNAs, 21 DEmiRNAs, and 15 DEcircRNAs. Among this network, the expression of hsa-miR-139-5p was negatively correlated with CDCA8, KPNA2, PRC1 or TOP2A. Hsa-miR-139-5p low or targeted DEmRNA high expressio...